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Objective:To investigate the clinical characteristics and prognosis of cryptococcal meningitis patients with anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies.Methods:A total of 216 non-acquired immunodeficiency syndrome (AIDS) related cryptococcal meningitis cases with positive cultures of Cryptococcus, hospitalized at Huashan Hospital, Fudan University during January 2014 and December 2021, were retrospectively included. The serum anti-GM-CSF autoantibodies were detected by enzyme linked immunosorbent assay, and the clinical characteristics and prognosis were compared between patients with and without anti-GM-CSF autoantibodies. Statistical comparisons were mainly performed using the chi-square test or Fisher′s exact test. Cox proportional-hazards model was used to analyze the risk factors associated with prognosis. Results:Among 216 enrolled patients, 23 patients were positive of anti-GM-CSF autoantibodies, with a positive rate of 10.6%. Among 23 patients, seven cases were infected with Cryptococcus gattii, and 16 cases were infected with Cryptococcus neoformans. In the group with positive anti-GM-CSF autoantibodies, 30.4%(7/23) of the patients were infected with Cryptococcus gattii, which was higher than that of 1.6%(3/193) in the group with negative anti-GM-CSF autoantibodies, and the difference was statistically significant ( χ2=38.82, P<0.001). In the group with positive anti-GM-CSF autoantibodies, 30.0% (6/20) had mass lesions with a diameter greater than three centimeters in the lungs, and the one-year all-cause mortality rate was 50.0% (10/20), which were both higher than those of 3.4%(5/145) and 16.1% (29/180) in the negative group, respectively. The differences were both statistically significant (both Fisher′s exact test, P<0.01). Age≥60 years (hazard ratio ( HR)=4.146, P=0.002), predisposing factors ( HR=3.160, P=0.021), epilepsy ( HR=6.129, P=0.002), positive anti-GM-CSF autoantibodies ( HR=2.675, P=0.034), white blood cell count of cerebrospinal fluid (CSF)<100 ×10 6/L ( HR=2.736, P=0.039), the titers of cryptococcal capsular polysaccharide antigen of CSF≥1∶1 280 ( HR=4.361, P=0.009) were independent risk factors for one-year all-cause mortality in patients with cryptococcal meningitis. Conclusions:In non-AIDS related cryptococcal meningitis patients, the positive rate of serum anti-GM-CSF autoantibodies is as high as 10.6%. Patients with anti-GM-CSF autoantibodies could be infected with both Cryptococcus neoformans and Cryptococcus gattii, and they have higher proportion of lung mass lesions than patients with negative anti-GM-CSF autoantibodies. The one-year survival rate decreases significantly in patients with anti-GM-CSF autoantibodies, which is an independent risk factor for the prognosis of cryptococcal meningitis.
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【Objective】 To investigate the significance of granulocyte macrophage colony-stimulating factor (GM-CSF), nerve growth factor (NGF) and interleukin-17 (IL-17) in the prostate tissue of rats with experimental autoimmune prostatitis(EAP). 【Methods】 EAP rat models were established and divided into control group, EAP group, anti-GM-CSF group (blocking control group) and anti-GM-CSFEAP group (blocking EAP group). Pain behaviors were tested. The pathological changes were observed with HE staining. The mRNA and protein expressions of GM-CSF, NGF and IL-17 were detected with RT-PCR and Western blot. 【Results】 Pain test showed the anti-GM-CSF group had less chronic pelvic pain than the EAP group. HE staining showed the anti-GM-CSF group had less tissue inflammatory response. The EAP inflammation score was higher in the control group than in the anti-GM-CSF group. Immunohistochemistry showed GM-CSF was positive in the EAP group (mainly in the nucleus). RT-PCR and Western blot results showed the mRNA and protein expressions of IL-17 and NGF significantly decreased 50 days after EAP in the anti-GM-CSF group. 【Conclusion】 Increased expressions of GM-CSF, NGF and IL-17 in prostate tissue of EAP rats may be important inflammatory mediators of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS);decreased expressions of NGF and IL-17 after resistance against GM-CSF indicate that GM-CSF may be a potential therapeutic target for CP/CPPS.
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BackgroundThe etiopathogenesis of major depressive disorder （MDD） is strongly associated with neuroinflammation. MDD is a highly heterogeneous psychiatric disorder， and the disease subtyping is an essential step for the identification of biological markers. The presence of psychomotor retardation seriously affects the prognosis of MDD， whereas the underlying mechanism is not yet completely clear. A potential involvement of granulocyte colony-stimulating factor （G-CSF） and macrophage colony-stimulating factor （M-CSF） in the pathogenesis of MDD with psychomotor retardation has been suggested in previous studies， but little detailed research has been completed. ObjectiveTo analyze the correlation of plasma G-CSF and M-CSF levels with psychomotor retardation in patients with MDD， and to explore the potential biological underpinnings of psychomotor retardation in MDD. MethodsA total of 50 MDD patients who met the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） and attended the outpatient clinics of Shanghai Mental Health Center from April 2018 to April 2019 were included. The severity of symptoms was assessed using the Hamilton Depression Scale-17 item （HAMD-17）. According to the retardation factor in HAMD-17， patients with a score of ≥8 were included in retardation group （n=22）， and those with a score below 8 were included in non-retardation group （n=28）. Another 22 age- and sex-matched healthy controls were concurrently recruited. Plasma G-CSF and M-CSF levels were measured in all subjects using Luminex liquid suspension chip technology. Spearman correlation analysis was adopted to verify the correlation of retardation factor score in HAMD-17 with plasma G-CSF and M-CSF levels in MDD patients. ResultsPlasma G-CSF levels were decreased in MDD patients compared with healthy controls ［57.34（39.24， 83.15）pg/mL vs. 71.47（61.20， 79.99）pg/mL， Z=-2.098， P<0.05］. A statistical difference was found in plasma G-CSF level ［63.92（54.60， 89.43）pg/mL vs. 47.80（33.41， 74.66）pg/mL vs. 71.47（61.20， 79.99）pg/mL， H=8.247， P=0.016］ and plasma M-CSF level ［20.05（16.05， 22.23）pg/mL vs. 13.05（11.43， 17.50）pg/mL vs. 18.95（14.59， 22.88）pg/mL， H=7.620， P=0.022］ among retardation group， non-retardation group and healthy control group. The post hoc pairwise comparisons using Bonferroni correction indicated that plasma G-CSF level was lower in non-retardation group compared with healthy control group （adjusted P<0.05）， and plasma M-CSF level was higher in retardation group compared with non-retardation group （adjusted P<0.05）. The retardation factor score in HAMD-17 was positively correlated with plasma M-CSF level in MDD patients （r=0.348， P<0.05）. ConclusionThe prevalence of psychomotor retardation in MDD patients may be related to abnormally elevated plasma M-CSF level. ［Funded by Shanghai "Science and Technology Innovation Action Plan" Project in Medical Innovation Research Field （number， 21Y11905600）； Shanghai "Science and Technology Innovation Action Plan" Project in Natural Science Field （number， 21ZR1455100）； Shanghai Mental Health Center Scientific Research Project （number， 2021-YJ02）］
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ObjectiveTo investigate whether there exists gender differences in mechanical pain hypersensitivity induced by the subcutaneous injection of macrophage colony-stimulating factor （M-CSF） in normal mice and to explore the preliminary mechanism. MethodsThirty 10-week-old C57BL/6J mice were randomly divided into three groups， (n = 10 mice/group, half male and half female). The albumin control group （BSA， 0.3 μg）， low dose M-CSF group （L M-CSF， 0.075 μg） and high dose M-CSF group （H M-CSF， 0.3 μg） received 50 μL BSA or M-CSF injected subcutaneously into the left medial thigh once daily for 3 consecutive days. Before and after drug administration， von-Frey mechanical sensitivity test was used to detect the mechanical paw withdrawal threshold （PWT） in each group. Immunofluorescence was performed to examine the expression changes of Ionized calcium-binding adaptor molecule 1 (Iba1) in skin， calcitonin gene-related peptide （CGRP） and phosphorylated ERK1/2 （p-ERK） in L5-L6 DRG and lumbar spinal dorsal horn. ResultsIn female mice， only high dose of M-CSF caused mechanical allodynia， whereas in male mice both doses produced marked allodynia. Mechanically， high-dose M-CSF induced massive aggregation of subcutaneous macrophages （marked by Iba1） in male and female mice， but more dramatic dependence in female mice. Similar gender differences were also found in the increase of p-ERK and CGRP expression in dorsal root ganglion （DRGs）. Notably， CGRP expression was especially elevated in the fibers of DRG in male mice. Correspondingly， the expressions of p-ERK and CGRP+ terminals in the superficial spinal dorsal horn of male mice were significantly higher than those of female mice after M-CSF treatment. ConclusionSubcutaneous injection of M-CSF triggers sexual dimorphism in mechanical pain hypersensitivity, which is related with differential changes in peripheral macrophage expansion and sensitization of the nociceptive pathway.
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Objective:To explore the efficacy of subcutaneous injection of granulocyte-macrophage colony-stimulating factor (GM-CSF) in preventing invasive fungal disease (IFD) in patients with multiple myeloma (MM).Methods:The clinical data of 222 patients who were admitted to the Second Hospital of Harbin Medical University from January 2015 to June 2021 were retrospectively analyzed. The patients was given GM-CSF (3-5 μg·kg -1·d -1, GM-CSF group) or granulocyte colony-stimulating factor (G-CSF, 2-5 μg·kg -1·d -1, G-CSF group) when neutrophils (ANC) ≤1.5×10 9/L after induction chemotherapy. Patients were discontinued when white blood cell count (WBC) ≥10.0×10 9/L. The incidence of IFD (including confirmed, clinical and proposed diagnosis) and breakthrough invasive fungal infections was compared between the two groups. Results:The incidence of IFD was 8.1% (18/222) in all patients. The incidence of IFD was 3.5% (3/85) and 10.9% (15/137) in the GM-CSF and G-CSF groups, respectively, and the difference between the two groups was statistically significant ( χ2 = 3.88, P = 0.049). In 9 patients of GM-CSF group receiving fungal infection prophylaxis and in 15 patients of G-CSF group receiving fungal infection prophylaxis, the incidence of breakthrough invasive fungal infections was 0 and 7 cases, respectively, and the difference between the two groups was statistically significant ( P = 0.022). Conclusions:GM-CSF application in MM patients can reduce the incidence of IFD and breakthrough invasive fungal infections.
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Abstract Objective The use of granulocyte macrophage colony-stimulating factor (GM-CSF)-containing medium, which is a commercial medium that is used for cultivation of embryos in in vitro fertilization (IVF) treatments, has been suggested to increase the efficiency of this procedure in patients with previous multiple unsuccessful attempts. In this retrospective study, we analyzed GM-CSF-containing embryo culture media compared with traditional culture media in terms of development of embryos, pregnancy, and ongoing pregnancy success and live birth rates. Methods This is a prospective case control study conducted in a single center. A total of 131 unexplained infertility patients were included in the study. A cohort of 69 patients whose embryos were cultured in GM-CSF-containing medium and a control group of 62 age-matched patients whose embryos were cultured in conventional Sage One Step medium were included in the study. The major study outcomes were achievement of pregnancy and ongoing pregnancy rate at 12 weeks of gestation. Results The pregnancy and ongoing pregnancy rates of the patients whose embryos were cultured in GM-CSF-containing medium were 39.13% and 36.23%, respectively. These were higher than the rates of the control group, which were 30.65% and 29.03%, respectively, although this difference was not statistically significant. In addition, the 5th-day embryo transfer percentage in the GM-CSF group was higher than in the control group (34.78% versus 27.4%). Conclusion The main findings of our study were that there was no difference between the GM-CSF-enhanced medium and the control group in terms of our major study outcomes. However, blastomere inequality rate and embryo fragmentation rates were lower in the GM-CSF group.
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Humans , Female , Adult , Fertilization in Vitro , Granulocyte-Macrophage Colony-Stimulating Factor , Embryo Culture Techniques , Embryo TransferABSTRACT
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multifunctional hematopoietic growth factor that can promote the recovery of leukopenia caused by tumor chemoradiotherapy, and can also prevent chemoradiotherapy-induced mucositis by promoting a variety of cells such as endothelial cells, epithelial cells, keratinocytes and fibroblasts. This article reviews the domestic and foreign basic and clinical research progress of GM-CSF in recent years, and discusses the mechanism and clinical application of GM-CSF as a mucosal repair agent in the prevention and treatment of tumor chemoradiotherapy-induced mucositis.
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Objective:To explore the efficacy and safety of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and human granulocyte colony-stimulating factor (G-CSF) for the prevention of post-chemotherapy infections in pediatric hematologic neoplasms.Methods:A total of 134 children hospitalized for chemotherapy in 6 tertiary hospitals from July 2016 to June 2018 were collected, including 60 cases in Children's Hospital of Fudan University, 38 cases in Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 29 cases in Children's Hospital Affiliated to Soochow University, 4 cases in the Affiliated Hospital of Qingdao University, 2 cases in Northwestern Women and Children's Hospital, and 1 case in Shandong Provincial Qianfoshan Hospital. The children were divided into GM-CSF group (38 cases), G-CSF group (45 cases) and GM-CSF+G-CSF group (51 cases) by using random number table method. The incidence of infections, the recovery time of absolute neutrophil counting (ANC), the decrease of blood platelet count (Plt) and the incidence of adverse reactions were compared among the three groups.Results:In all children, a total of 64 cases (47.8%) had infections during the myelosuppression phase after chemotherapy, of which 18 cases (47.4%) in GM-CSF group, 20 cases (44.4%) in G-CSF group, and 26 cases (51.0%) in GM-CSF+G-CSF group. The incidence of respiratory infection in G-CSF group was higher than that in GM-CSF group and GM-CSF+ G-CSF group [22.2% (10/45) vs. 2.6% (1/38), 4.0% (2/51), χ2 = 12.00, P = 0.002]. The median time to recovery of ANC > 1.5×10 9/L was 10.5 d (8 d, 15 d) in all children, 12 d (10 d, 16 d) in GM-CSF group, 9 d (8 d, 12 d) in G-CSF group, and 10 d (8 d, 16 d) in GM-CSF+G-CSF group. In all children, a total of 101 cases (75.4%) had Plt<50×10 9/L during the myelosuppression phase, and 79 cases (59.0%) had Plt <20×10 9/L. The differences in the incidence of Plt <50×10 9/L and <20×10 9/L among the three groups were not statistically significant (both P > 0.05). In all children, the adverse reactions occurred in 24 cases (17.9%), including 20 cases (14.9%) of fever, 2 cases (1.5%) of sore throat, 1 case (0.7%) of nausea, and 1 case (0.7%) of diarrhea; no adverse reactions of grade 2 or above occurred. The difference in the incidence of adverse reactions among the three groups was not statistically significant ( P>0.05). Conclusions:The efficacy of GM-CSF and G-CSF for the prevention of infections in pediatric hematologic neoplasms during the myelosuppression phase after chemotherapy is roughly equivalent, and combination of both has a good tolerance. The incidence of respiratory infection using GM-CSF alone or GM-CSF+G-CSF is low, which might benefit from the effect of GM-CSF on lung infections.
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Objective:To investigate the expression and significance of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with acute respiratory distress syndrome (ARDS).Methods:The clinical data of 81 patients with ARDS who received treatment between February 2018 and July 2020 in Linhai Second People's Hospital, China (group A) and 69 healthy controls who concurrently received physical examination (group B) were retrospectively analyzed. Serum levels of G-CSF, GM-CSF and oxygenation index (OI) measured before treatment in the group A were compared with the levels measured in the control group. Serum levels of G-CSF and GM-CSF measured before treatment were compared between patients with different disease severities in the group A. The correlation between serum G-CSF and GM-CSF levels and disease condition was analyzed. The significance of serum G-CSF and GM-CSF levels in the diagnosis of ARDS was investigated.Results:Before treatment, serum G-CSF and GM-CSF levels in the group A were (201.89 ± 19.44) ng/L, (48.95 ± 6.03) ng/L, respectively, which were significantly higher than those in the group B [(38.13 ± 5.22) ng/L, (7.71 ± 0.92) ng/L, t = 67.889, 56.228, both P < 0.001]. OI in the group A was significantly lower than that in the group B [(159.09 ± 16.81) mmHg vs. (385.13 ± 20.34) mmHg, t = 74.519, P < 0.001). In group A, serum levels of G-CSF and GM-CSF were (271.99 ± 23.15) ng/L and (65.07 ± 8.38) ng/L respectively in patients with severe acute respiratory distress syndrome ( n = 13), (203.14 ± 18.36) ng/L and (50.91 ± 7.18) ng/L respectively in patients with moderate acute respiratory distress syndrome ( n = 30), and (176.92 ± 15.98) ng/L and (41.89 ± 6.02) ng/L, respectively in patients with mild acute respiratory distress syndrome ( n = 38). There was significant difference among patients with severe, moderate and mild acute respiratory distress syndrome ( F = 133.201, 57.116, both P < 0.05). Serum levels of G-CSF and GM-CSF in group A were negatively correlated with OI ( r = -0.819, -0.824, both P < 0.05). The area under the receiver operating characteristic curve of serum levels of G-CSF and GM-CSF and their combination were 0.780 (95% CI: 0.628-0.933), 0.752 (95% CI: 0.590-0.913) and 0.912 (95% CI: 0.835-0.989), respectively. The Youden index was 0.686, 0.696 and 0.739, respectively. The area under the receiver operating characteristic curve and the Youden index of the combined detection of serum levels of G-CSF and GM-CSF were highest. Conclusion:Serum levels of G-CSF and GM-CSF in patients with ARDS were higher than those in healthy controls. Higher serum levels of G-CSF and GM-CSF led to more severe disease condition. Serum levels of G-CSF and GM-CSF in combination has a higher value in the diagnosis of ARDS than serum levels of G-CSF and GM-CSF alone.
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Objective@#To investigate the effects of macrophage colony-stimulating factor (M-CSF) on the polarization and infiltration of M2 macrophages and the invasion and metastasis of tumor cells in ovarian cancer microenvironment. @*Methods@#A co-culture system consisting of ovarian cancer cells (A2780 and SKOV3) and THP-1 derived macrophages was established in vitro. The M-CSF levels in culture medium and M-CSF mRNA levels in cancer cells and macrophages were detected by ELISA and qRT-PCR, respectively. The proportion of CD68+CD163+ M2 macrophages (polarization cells) was determined by flow cytometry. The invasive and metastatic ability of A2780 and SKOV3 cells after co-culturing with M2 macrophages were analyzed using Transwell assay. The expression levels of M-CSF, CD68+, CD163+ and E-cad in paraffin sections of 52 patients with ovarian cancer and 18 patients with benign ovarian tumor were detected by the immunohistochemistry staining, and their correlations and the relationship between M-CSF and clinicopathological features of ovarian cancer patients were analyzed. @*Results@#The M-CSF levels in culture medium of the co-culture group (A2780 and SKOV3 cells co-cultured with M2 macrophages) were significantly higher than that of A2780 and SKOV3 cells alone (t=14.315 and 12.338, P＜0.01). Fluorescence quantitative PCR results showed that the increased M-CSF originated from the secretion of co-cultured ovarian cancer cells (t=29.915 and 36.826, P＜0.01). The proportions of CD68+CD163+ M2 macrophages in the A2780 cells co-cultured with M2 macrophages group and SKOV3 cells co-cultured with M2 macrophages group were (6.14±0.50)% and (7.32±0.67)%, respectively, which were significantly higher than that in the M2 macrophages alone group ([1.82±0.34]%, t=12.289 and 12.711, P＜0.01). Transwell assay showed that the co-culture environment enhanced the invasion of A2780 and SKOV3 cells (24.00±4.81 vs 75.20±6.42, t=11.058; 18.40±2.31 vs 61.60±9.66, t=7.537, P＜0.01). The expression levels of M-CSF in ovarian cancer tissues were positively correlated with the number of CD68+ cells and CD163+ cells (r=0.690 and 0.596, P＜0.01), and negatively with the expression levels of E-cad (r=-0.566, P＜0.01). Moreover, the expression levels of M-CSF and the number of CD68+ cells and CD163+ cells in ovarian cancer tissues were significantly higher than that in benign ovarian tumor tissues, however, the expression levels of E-cad were on the contrary. The expression levels of M-CSF in ovarian cancer tissues were significantly correlated with tumor stage, differentiation and lymphatic node metastasis (χ2=6.240, 6.612 and 4.544, respectively, P＜0.05). @*Conclusion@#The increased expression of M-CSF in ovarian cancer microenvironment may induce the polarization and infiltration of CD68+CD163+ M2 macrophages, and then promote the invasion and metastasis of ovarian cancer cells.
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Objective: To investigate the effect of macrophage colony-stimulating factor-1 (CSF-1) expression in osteosarcoma cells on tumor angiogenesis, and to explore its possible mechanism. Methods: The expressions of CSF-1 and allograft inflammatory factor-1 (AIF-1) in human osteoblasts hFOB1.19, osteosarcoma SAOS-2, MG-63 and U2OS cells were detected by Western blotting. The expressions of AIF-1 and Ras-related C3 botulinum toxin substrate-1 (Rac-1) in osteosarcoma SAOS-2 cells after transfection with siRNA-CSF-1 or siRNAnegative control (siRNA-NC) were detected by Western blotting. The culture supernatant was collected after siRNA-CSF-1 or siRNA-NC was transfected into osteosarcoma SAOS-2 cells, the untransfected SAOS-2 cells were used as the blank control (BC). Then the collected culture supernatant was mixed with the complete medium at a volume ratio of 1∶1 to make the conditioned medium for the culture of human umbilical vein endothelial cells (HUVECs). After treatment with the siRNA-CSF-1 or siRNA-NC conditional medium, the proliferation, migration and tube formation of HUVECs were detected by MTT assay, Transwell chamber assay and tube formation experiment, respectively; The expressions of vascular endothelial growth factor (VEGF) and Rac-1 in HUVECs were detected by Western blotting. After HUVECs were treated with siRNA-CSF-1 conditional medium combined with 0.1% DMSO or Rac-1 activator phorbol 12-myristate 13-acetate (PMA) for 24 h, the cell proliferation, migration and the tube formation were detected by MTT assay, Transwell chamber assay and tube formation experiment, respectively; The expressions of VEGF and Rac-1 in HUVECs were detected again by Western blotting. Results: The expression levels of CSF-1 and AIF-1 proteins in osteosarcoma SAOS-2, MG-63 and U2OS cells were higher than those in osteoblasts hFOB1.19 (all P < 0.05). The expressions of CSF-1 and AIF-1 were positively correlated (R2 = 0.492 2, P = 0.001 2). The expression levels of AIF-1 and Rac-1 in osteosarcoma SAOS-2 cells of siRNA-CSF-1 transfection group were down-regulated (both P < 0.05). After treatment with siRNA-CSF-1 conditional medium, the proliferation, migration and tube formation abilities of HUVECs were decreased (all P < 0.05), and the expression levels of VEGF and Rac-1 were down-regulated (both P < 0.05). Whereas Rac-1 activator reversed the effects of siRNA-CSF-1 conditional medium on the proliferation, migration, tube formation as well as VEGF and Rac-1 expressions of HUVECs (all P < 0.05). Conclusion: CSF-1 in osteosarcoma cells may promote the tumor angiogenesis by AIF-1/ Rac-1 pathway.
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Objective To study the differentiation types of microglia induced by macrophage colony-stimulating factor (M-CSF).Methods Rat microglia cultured in vitro were inoculated on 6-well plates and divided into 3 groups (n=4 each) using a random number table method when cell confluence reached 70％:blank control group (C group),vehicle control group (P group) and M-CSF group.Group P was incubated with phosphate buffer solution for 7 days and group M-CSF with 20 ng/ml M-CSF for 7 days.The expression of a specific M1 phenotype marker tumor necrosis factor-alpha (TNF-α) and specific M2 phenotype markers interleukin-10 (IL-10) and brain-derived neurotrophic factor (BDNF) was determined by Western blot.Results Compared with C group,the expression of IL-10 and BDNF was significantly upregulated (P＜0.05),and no significant change was found in TNF-α expression in M group (P＞0.05),and no significant change was found in the expression of TNF-α,IL-10 or BDNF in P group (P＞0.05).Conclusion M-CSF can induce microglia to differentiate into a M2 phenotype.
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Objective To investigate the expression and clinical significance of macrophage colony stimulating factor ( M?CSF ) and tumor necrosis factor α ( TNF?α ) in placenta of early onset severe preeclampsia (PE)??Methods Immunohistochemical SP method was used to detect the expression of M?CSF and TNF?α in 77 cases paraffin specimens from Department of Pathology,First Affiliated Hospital of Henan University of Science and Technology from September 2015 to September 2017,including 35 cases of early?onset severe PE,42 cases of late?onset severe PE and 30 cases of normal pregnant women??Results (1)The positive expression rates of M?CSF in control group,late?onset severe PE group and early?onset severe PE group were 30%(9／30),61??90%(26／42),82??86%(29／35),respectively??The difference was statistically significant ( χ2 ＝ 18??90, P＜0??05)??The positive expression rates of early?onset severe PE group were significantly higher than those in control group (χ2＝18??59,P＜0??05),and the difference was statistically significant????The positive expression of early?onset severe PE group was higher than that of late?onset severe PE group,and the difference was statistically significant (χ2＝4??017,P＜0??05)??(2) The positive expression rates of TNF?α in control group,late?onset severe PE group and early?onset severe PE group were 33??33%(10／30),69??05%(29／42),91??43%(32／35),respectively??The difference was statistically significant (χ2＝30??21,P＜0??05)??The positive expression of TNF?α in early?onset severe PE group was significantly higher than that in control group (χ2＝21??37,P＜0??05),and the difference was statistically significant??The positive expression of M?CSF and TNF?a in early?onset severe PE group was higher than that in late?onset severe PE group,and the difference was statistically significant (χ2＝4??529,P＜0??05); (3) The expression of M?CSF and TNF?α was positively correlated in PE (r＝0??441,P＝0??000)??Conclusion Placental damage is higher in early?onset severe PE,and is related to the severity of the disease??The levels of M?CSF and TNF?alpha in placenta of PE patients may play a synergistic role in the occurrence and development of PE??
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BACKGROUND: This study was conducted to investigate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the mobilization of mesenchymal stem cells (MSCs) from the bone marrow (BM) into the peripheral blood (PB) in rats. METHODS: GM-CSF was administered subcutaneously to rats at 50 µg/kg body weight for 5 consecutive days. The BM and PB of rats were collected at 1, 3, and 5 days during the administration for analysis. RESULTS: Upon GM-CSF administration, the number of mononuclear cells increased rapidly at day 1 both in the BM and PB. This number decreased gradually over time in the BM to below the initial amount by day 5, but was maintained at a high level in the PB until day 5. The colony-forming unit-fibroblasts were increased in the PB by 10.3-fold at day 5 of GM-CSF administration, but decreased in the BM. Compared to GM-CSF, granulocyte-colony stimulating factor (G-CSF) stimulated lower levels of MSC mobilization from the BM to the PB. Immunohistochemical analysis revealed that GM-CSF induced a hypoxic and proteolytic microenvironment and increased C-X-C chemokine receptor type 4 (CXCR4) expression in the BM. GM-CSF added to BM MSCs in vitro dose-dependently increased CXCR4 expression and cell migration. G-CSF and stromal cell derived factor-1 (SDF-1) showed similar results in these in vitro assays. Know-down of CXCR4 expression with siRNA significantly abolished GM-CSF- and G-CSF-induced MSC migration in vitro, indicating the involvement of the SDF-1-CXCR4 interaction in the mechanism. CONCLUSION: These results suggest that GM-CSF is a useful tool for mobilizing BM MSCs into the PB.
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Animals , Rats , Hypoxia , Body Weight , Bone Marrow , Cell Movement , Granulocyte Colony-Stimulating Factor , Granulocyte-Macrophage Colony-Stimulating Factor , In Vitro Techniques , Mesenchymal Stem Cells , RNA, Small Interfering , Stromal CellsABSTRACT
La Proteinosis Alveolar Pulmonar (PAP) es una enfermedad poco frecuente, caracterizada por la acumulación de material lipoproteico derivado del surfactante pulmonar al interior de los alvéolos por una falla de depuración de este material por los macrófagos alveolares, siendo la causa más frecuente de esta disfunción la acción bloqueadora producida por anticuerpos anti factor estimulante de colonias de granulocitos y macrófagos (GM-CSF) lo que lleva a un deterioro del intercambio gaseoso. La evolución es variable abarcando desde la resolución espontánea hasta la insuficiencia respiratoria grave y la muerte. Se describen tres formas de PAP: Genética, secundaria y autoinmune (antes primaria o idiopática) siendo esta última la más frecuente en adultos. Clínicamente, se manifiesta por disnea, tos seca e hipoxemia que pueden ser progresivas. En la radiografía de tórax se encuentran opacidades bilaterales y la tomografía computarizada de tórax de alta resolución (TACAR) muestra vidrio esmerilado con sobre posición de engrosamiento septal intra e interlobulillar, patrón conocido como "crazy paving". El diagnóstico se basa en la clínica y en el lavado broncoalveolar con material PAS positivo. La biopsia quirúrgica es confirmatoria. El tratamiento clásico es el lavado pulmonar total (LPT) para remover el contenido alveolar. Otras alternativas son la administración de GM-CSF subcutáneo o inhalado, plasmaferesis y rituximab, cuyos resultados son variables. Diferentes autores han modificado la forma del LPT y combinado los diferentes métodos de tratamiento con el fin de obtener resultados más rápidos y efectivos.
Pulmonary Alveolar Proteinosis (PAP) is a rare disease characterized by the accumulation of surfactant derived lipoproteinaceous material filling the alveoli, secondary to failure of its clearance by macrophages. Most of the patients are adults that have auto antibodies directed to Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF). The evolution is towards disturbed gaseous exchange with a wide spectrum of disease from spontaneous recovery to death. There are three forms of PAP: genetic, secondary and autoimmune. Symptoms are scarce and patients may present with dyspnea, dry cough and hypoxemia. Chest X ray shows bilateral opacities and thorax CT depicts ground glass opacities surrounded by septal widening, the so called "crazy paving" pattern. Diagnosis is made on clinical and radiological grounds and confirmed by PAS positive staining of bronchoalveolar lavage material or surgical lung biopsy. Accepted treatment is whole lung lavage (WLL) with saline. Alternatives are subcutaneous or inhaled GM-CSF, Plasmapheresis or Rituximab, and even modification of the method of WLL and combination of different manner of treatment.
Subject(s)
Humans , Pulmonary Alveolar Proteinosis/diagnosis , Pulmonary Alveolar Proteinosis/therapy , Pulmonary Alveolar Proteinosis/etiology , Pulmonary Surfactants/therapeutic use , Granulocyte-Macrophage Colony-Stimulating Factor , Plasmapheresis , Bronchoalveolar Lavage , Rituximab/therapeutic useABSTRACT
@#Objective: To prepare the fusion protein mGM-CSF-GnRH3 (mGGn) of mouse granulocyte-macrophage colony stimulating factor (mGM-CSF) combining with gonadotropin releasing hormone (GnRH) and the fusion protein mGM-CSF-GRP6 (mG6) of mGM-CSF combining with gastrin-releasing peptide (GRP), and to investigate the inhibitory effect of the above two fusion proteins on B16F10 melanoma in vitro as well as to preliminarily predict their isoelectric point, relative molecular weight, hydrophobicity, stability, subcellular localization, signal peptide, spatial structure and potential epitopes. Methods:After the successful preparation of mGGn and mG6, the effects of different concentrations of fusion proteins on tumor cell morphology, migration, proliferation and cell cycle were detected by microscopic observation, scratch test, CCK-8 method and flow cytometry, respectively. The protein online analysis systems EXPASY, GOR4, SWISS MODEL were used to predict the basic properties and secondary/tertiary structure of recombinant fusion proteins. The B cell epitopes were predicted by IEDB and ABCpred software, the CTL epitopes were comprehensively predicted by SYFPEITHI, BlMAS and NetCTL software, and the Th epitopes were predicted by NetMHCIIpan 3.1 Server and IEDB software. Results:Both mGGn and mG6 inhibited the migration and proliferation of tumor cells. mGGn could block B16F10 cell cycle at G1 phase while mG6 could block B16F10 cell cycle at S phase, all of which prevented cells entering into G2 phase to inhibit tumor cell growth. The mGGn and mG6 fusion proteins got diverse structures and had multiple potential B epitopes, CTL epitopes and Th epitopes. Conclusion: mGGn and mG6 have inhibitory effect on B16F10 melanoma in vitro, and bioinformatics predictions have laid a foundation for further study of the biological functions and immunological activities of these fusion proteins.
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Objective: To compare the efficacy between chemotherapy plus granulocyte colony-stimulating factor (G-CSF) and chemotherapy plus G-CSF and granulocyte-macrophage colony-stimulating factor (GM-CSF) for the mobilization of peripheral blood stem cells (PBSC) and hematopoietic recovery after transplantation in patients with multiple myeloma (MM). Methods: A retrospective study of autologous PBSC (APBSC) mobilization data of 56 MM patients who were treated with chemotherapy plus G-CSF or chemotherapy plus G-CSF and GM-CSF from May 2008 to July 2016 in Tianjin Medical University Cancer Institute and Hospital was conducted. The mobilization efficacy and hematopoietic recovery were analyzed. Results: In the univariate analysis, the successful collection rate of a single harvest in women and in patients with ISS stage Ⅲ and R-ISS stage Ⅱ/Ⅲ and treated with chemotherapy plus G-CSF was lower (P<0.05). However, age (≤60 years vs.>60 years), subtype, D-S staging (Ⅰ+Ⅱvs.Ⅲ), number of cycles of chemotherapy before mobilization (≤6 cycles vs.>6 cycles), disease phase before mobilization (PR vs. CR), and interval between diagnosis and mobilization (≤18 months vs.>18 months) were not correlated with CD34+ cell collection and successful mobilization rates (P>0.05). In the multivariate model, the successful mobilization rate in patients who received the chemotherapy plus G-CSF and GM-CSF mobilization regimen was higher (OR=12.009, 95% CI=1.961-73.537). The effect of mobilization regimens remained significant (P=0.007). Hematopoietic recovery without transplantation-related mortality occurred successfully in all patients. Conclusions: Chemotherapy plus G-CSF and GM-CSF mobilization regimens can significantly increase the effect of APBSC mobilization and ensure the recovery of hematopoietic function after transplantation. Chemotherapy plus G-CSF and GM-CSF mobilization regimens are safe and effective for mobilizing APBSCs.
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The granulocyte-macrophage colony-stimulating factor(GM-CSF)can effectively induce the proliferation of tumor-associat-ed immunocytes as a hematopoietic factor;therefore,the fact that GM-CSF can induce systemic antitumor immune responses has at-tracted much attention.Radiotherapy,as one of the main treatment approaches of cancer,can kill tumor cells directly,and has an ef-fect on anti-tumor immunity.Several clinical studies have shown that radiotherapy combined with the GM-CSF can induce an abscopal effect and confer favorable therapeutic effects for cancer.Herein,we review the research progress on GM-CSF,and radiotherapy com-bined with GM-CSF in tumor treatment.
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Objective To observe the effectiveness and safeness of granulocyte macrophage colony stimulating factor (GM-CSF)and whole lung lavage therapy for patients with idiopathic pulmonary alveolar proteinosis(IPAP).Methods Two IPAP patients who were hospitalized in Changhai Hospital from August 2015 to March 2017 were enrolled for the study.Both patients were treated with GM-CSF therapy after whole lung lavage.One patient received GM-CSF by subcutaneous injection and the other by inhalation.Results Both patients'conditions were improved after GM-CSF and whole lung lavage therapy. Conclusion Treatment with subcutaneous injection or inhalation of granulocyte macrophage colony stimulating factor and whole lung lavage is safe and effective for IPAP patients.
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Objective To study effects of secreted cytotoxic T-lymphocyte-associated protein-4(CTLA-4)fusion Plasmodium falciparum DNA vaccine combined with granulocyte-macrophage colony stimulating factor(GM-CSF) on humoral and cellular immune responses in mice.Methods The malaria antigen coding sequence fused with CTLA-4 extracellular region of mouse was constructed as eukaryotic secretory expression vector VR 1012-sES312-CTLA,recombinant protein in culture of transfected HEK 293 cells was detected by Western blot.Balb/c mice were co-administrated with VR1012-sES312-CTLA and GM-CSF expression vector.After immunization specific antibody IgG titers and cytokines IFN-γand IL-4 expression levels were evaluated by ELISA and ELISPOT respectively. Results The introduction of CTLA-4 into malaria DNA vaccine system and application of GM-CSF adjuvant signifi-cantly enhanced the specific immune response to the vaccine.Antibody titers in VR1012-sES312-CTLA and GM-CSF co-immunized mice showed a 190-fold increase compared with the simple designed VR1012-ES312 immunization(P<0.001).Conclusions Humoral and cellular immunity induced by malaria DNA vaccine are significantly en -hanced by both dendritic cell-targeting modification and the introduction of GM-CSF molecular adjuvant into the im-mune system.This result provides a new idea for effectively raising the immune response to malaria DNA vaccine.