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Prevention and treatment of complications after liver transplantation play a significant role in maintaining liver graft function and improving clinical prognosis of the recipients. Neutrophil extracellular trap (NET) are fibrous net-like structures composed of DNA as the skeleton and histones and granular proteins released by activated neutrophils. Studies have shown that the activation of neutrophils and the release of NET in donor liver after liver transplantation are involved in the incidence of multiple liver transplantation-related complications including ischemia-reperfusion injury, acute rejection, acute liver failure and recurrence of hepatocellular carcinoma, etc. In this article, the effect of NET on the complications after liver transplantation was mainly assessed, and research progress on NET as a potential target for the prevention and treatment of complications after liver transplantation was reviewed, aiming to provide reference for the prevention and treatment of complications after liver transplantation, enhance clinical efficacy of liver transplantation and improve clinical prognosis of the recipients.
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OBJECTIVES@#To study the changes in cell free-DNA (cf-DNA), a marker of neutrophil extracellular traps (NETs), in neonates with acute respiratory distress syndrome (ARDS), and to evaluate its relationship with the severity and early diagnosis of ARDS.@*METHODS@#The neonates diagnosed with ARDS in the Affiliated Hospital of Jiangsu University from January 2021 to June 2022 were enrolled in the prospective study. The neonates were divided into mild, moderate, and severe ARDS groups based on the oxygen index (OI) (4≤OI<8, 8≤OI<16, and OI≥16, respectively). The control group was selected from jaundice neonates who were observed in the neonatal department of the hospital during the same period, and they had no pathological factors causing neonatal jaundice. Peripheral blood samples were collected on day 1, day 3, and day 7 after admission for the ARDS group, and on the day of admission for the control group. Serum cf-DNA levels were measured using a fluorescence enzyme-linked immunosorbent assay. Serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels were measured using enzyme-linked immunosorbent assay. A Pearson correlation analysis was used to evaluate the correlation of serum cf-DNA levels with serum IL-6 and TNF-α levels.@*RESULTS@#A total of 50 neonates were enrolled in the ARDS group, including 15 neonates with mild ARDS, 25 with moderate ARDS, and 10 with severe ARDS. Twenty-five neonates were enrolled in the control group. Compared with the control group, the serum levels of cf-DNA, IL-6, and TNF-α in all ARDS groups were significantly increased (P<0.05). Compared with the mild ARDS group, the serum levels of cf-DNA, IL-6, and TNF-α in the moderate and severe ARDS groups were significantly increased (P<0.05), and the increase was more significant in the severe ARDS group (P<0.05). The serum levels of cf-DNA, IL-6, and TNF-α in all ARDS groups were significantly increased on day 3 after admission and significantly decreased on day 7 after admission compared with those on day 1 after admission (P<0.05). The Pearson correlation analysis showed that there was a positive correlation between serum cf-DNA levels and IL-6 levels as well as TNF-α levels in 50 neonates with ARDS (P<0.05).@*CONCLUSIONS@#There is an excessive expression of NETs in neonates with ARDS, and dynamic monitoring of serum cf-DNA levels has certain clinical value in evaluating the severity and early diagnosis of ARDS in neonates.
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Infant, Newborn , Humans , Extracellular Traps , Prospective Studies , Tumor Necrosis Factor-alpha , Interleukin-6 , Prognosis , ROC Curve , Respiratory Distress Syndrome, Newborn , DNAABSTRACT
Objective:To investigate the activation level of neutrophil extracellular trap (NET) in the bile of patients with choledocholithiasis and its clinical significance.Methods:From May 2021 to October 2022, 130 patients underwent endoscopic retrograde cholangiopancreatography (ERCP) at the Department of Gastroenterology, the First Affiliated Hospital of Anhui Medical University were enrolled. The patients were divided into choledocholithiasis group (90 cases) and non-choledocholithiasis group (40 cases), and the choledocholithiasis group was further divided into large stone group (maximum diameter >1 cm, 36 cases) and small stone group (maximum diameter≤1 cm, 54 cases). The bile samples were collected from 130 patients during operation and 16 choledocholithiasis patients with nasobiliary drainage at 24 h after operation.The levels of myeloperoxidase(MPO), neutrophilelastase(NE), and citrullinated histone H3(CitH3) in bile were detected by enzyme-linked immunosorbent assay.The levels of MPO, NE, and CitH3 were compared between choledocholithiasis group and non-choledocholithiasis group, between large stone group and small stone group, as well as between choledocholithiasis patients before ERCP and after ERCP. Mann-Whitney U test and Wilcoxon signed rank test were used for statistical analysis. Results:The levels of MPO, NE and CitH3 in the bile of choledocholithiasis group were 32.6 U/L(28.5 U/L), 30.6 ng/L(35.2 ng/L) and 0.37 μg/L(0.73 μg/L), respectively, which were all higher than those of non-choledocholithiasis group (19.9 U/L(36.4 U/L), 18.2 ng/L(27.4 ng/L), and 0.10 μg/L(0.25 μg/L)), and the differences were statistically significant ( Z=2.91, 3.20 and 3.34; P=0.004, 0.001 and 0.001). The levels of MPO, NE and CitH3 of large stone group were 47.0 U/L(49.4 U/L), 48.4 ng/L(39.5 ng/L) and 0.83 μg/L(1.08 μg/L), respectively, which were all higher than those of small stone group (29.3 U/L(17.5 U/L), 24.0 ng/L(25.8 ng/L), and 0.27 μg/L(0.45 μg/L)), and the differences were statistically significant ( Z=2.01, 3.58 and 3.63; P=0.044, <0.001 and <0.001). The levels of MPO, NE and CitH3 in the bile of choledocholithiasis patients after ERCP significantly decreased compare with those before ERCP (19.4 U/L(19.8 U/L) vs. 33.6 U/L(36.7 U/L), 12.7 ng/L(15.1 ng/L) vs. 22.7 ng/L(25.9 ng/L), 0.05 μg/L(0.12 μg/L) vs. 0.14 μg/L(0.27 μg/L)), and the differences were statistically significant ( Z=3.52, 3.30 and 3.18; all P<0.001). Conclusion:The activation level of NET in the bile of patients with choledocholithiasis increase, while the activation level of NET decrease after ERCP, which indicate that NET may be involved in the formation of choledocholithiasis.
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Ischemia-reperfusion injury (IRI) is a common pathophysiological phenomenon, secondary to multiple pathological processes, such as organ transplantation, acute kidney injury and myocardial infarction. IRI may significantly aggravate the severity of diseases and increase the fatality of patients. Aseptic inflammation is one of the critical mechanisms of IRI. Damage-associated molecular pattern (DAMP) is a pivotal substance, which mediates aseptic inflammation. After released into extracellular space, it could effectively activate the immune system, and initiate and maintain the inflammatory responses by binding with pattern recognition receptor (PRR). Neutrophil extracellular trap (NET) is a DNA-based network structure released by neutrophils during the process of inflammatory responses, which contains histones and multiple granular proteins. Recent studies have demonstrated that DAMP and NET may aggravate IRI via aseptic inflammation. In this article, relevant studies of DAMP, NET and their relationship in IRI were reviewed, which was of great significance for understanding the pathophysiological mechanism of IRI and studying the corresponding prevention and treatment strategies.
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Objective:To observe the effect of peripheral 5-hydroxytryptophan (5-HT)-induced neutrophil extracellular trap (NET) on lung injury in septic mice.Methods:Wild-type (WT type) and Tph1 knockout (KO) C57 mice (6-8 weeks) were selected and divided into WT mice sham group, WT mice sepsis group, Tph1 KO mice sham group and Tph1 KO mice sepsis group according to the random number table method. Mice in the sham group received sham surgery (only open the abdominal cavity to flip the cecum without ligation and puncture, and then close the abdominal cavity); the mice in the sepsis group received cecal ligation and puncture (CLP) to establish sepsis model. The mice were sacrificed 12 hours after the operation, and the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in bronchialalveolar lavage fluid (BALF) were detected by enzyme linked immunoadsordent assay (ELISA); at the same time, the lung tissues were collected, and the pathological changes of lung tissues were observed under light microscope, and the production of NET in lung tissues was observed by immunofluorescence microscope. Results:The pathological results suggested that the lung tissue structure in sham groups was intact without exudation, while the alveolar structures of mice in the sepsis groups were damaged, with obvious exudation in the alveolar cavity and thickened alveolar walls accompanied by a large number of inflammatory cell infiltration, and the degree of lung injury in the sepsis group of WT mice was more severe than that of the sepsis group of Tph1 KO mice. ELISA results showed that there was no statistically significant difference in the contents of TNF-α and IL-6 in mice BALF from different strains of the sham group; while the contents of TNF-α and IL-6 in BALF of septic mice group were significantly higher than those in sham group [WT mice: TNF-α (μg/L) was 158.20±28.46 vs. 14.00±3.28, IL-6 (μg/L) was 304.98±21.78 vs. 57.70±12.30; Tph1 KO mice: TNF-α (μg/L) was 85.88±20.13 vs. 14.95±1.53, IL-6 (μg/L) was 169.50±45.61 vs. 55.05±12.68, all P < 0.01], and the above index levels in the sepsis group of WT mice were significantly higher than the sepsis group of Tph1 KO mice [TNF-α (μg/L): 158.20±28.46 vs. 85.88±20.13, IL-6 (μg/L): 304.98±21.78 vs. 169.50±45.61, both P < 0.01]. Immunofluorescence staining showed that a very small amount of NET formation was detected in the mice lungs from the sham group; a large amount of NET formation was detected in the lung tissues in the sepsis group, which were significantly higher than those in sham group [WT mice: (34.75±7.27)% vs. (1.75±0.96)%, Tph1 KO mice: (14.25±5.74)% vs. (2.50±1.29)%, both P < 0.01], and the amount of NET produced in the lung tissues of the WT mice sepsis group was significantly higher than that of the Tph1 KO mice sepsis group [(34.75±7.27)% vs. (14.25±5.74)%, P < 0.01]. Conclusions:In sepsis, the increased production of inflammatory factors in the mice lung tissues induces to lung injury. The mechanism may relate to the increased production of NET in the lung tissues mediated by peripheral 5-HT synthesized by enterochromaffin cells and released into the blood; inhibiting the production of 5-HT in the peripheral blood can effectively reduce the production of NET in the lung tissues, thereby reducing lung injury.
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Cellular mechanics, a major regulating factor of cellular architecture and biological functions, responds to intrinsic stresses and extrinsic forces exerted by other cells and the extracellular matrix in the microenvironment. Cellular mechanics also acts as a fundamental mediator in complicated immune responses, such as cell migration, immune cell activation, and pathogen clearance. The principle of atomic force microscopy (AFM) and its three running modes are introduced for the mechanical characterization of living cells. The peak force tapping mode provides the most delicate and desirable virtues to collect high-resolution images of morphology and force curves. For a concrete description of AFM capabilities, three AFM applications are discussed. These applications include the dynamic progress of a neutrophil-extracellular-trap release by neutrophils, the immunological functions of macrophages, and the membrane pore formation mediated by perforin, streptolysin O, gasdermin D, or membrane attack complex.
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Microscopy, Atomic Force , NeutrophilsABSTRACT
The inflammatory response is an essential role of innate immune cells such as neutrophils, which plays an important role in the occurrence and development of inflammatory diseases. Neutrophil extracellular traps (NETs) are responsible for killing microorganisms and inducing the inflammatory response. We review the function of NETs in inflammatory diseases based on research publications since 2016. In addition, the ability of drugs that target NETs to ameliorate inflammation-related diseases is summarized. This review suggests a new strategy of targeting NETs for the treatment of inflammation-related diseases.
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Autophagy is a highly conserved intracellular degradation and energy-recycling mechanism that contributes to the maintenance of cellular homeostasis. Extensive researches over the past decades have defined the role of autophagy innate immune cells. In this review, we describe the current state of knowledge regarding the role of autophagy in neutrophil biology and a picture of molecular mechanism underlying autophagy in neutrophils. Neutrophils are professional phagocytes that comprise the first line of defense against pathogen. Autophagy machineries are highly conserved in neutrophils. Autophagy is not only involved in generalized function of neutrophils such as differentiation in bone marrow but also plays crucial role effector functions of neutrophils such as granule formation, degranulation, neutrophil extracellular traps release, cytokine production, bactericidal activity and controlling inflammation. This review outlines the current understanding of autophagy in neutrophils and provides insight towards identification of novel therapeutics targeting autophagy in neutrophils.
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Autophagy , Biology , Bone Marrow , Extracellular Traps , Homeostasis , Inflammation , Neutrophils , PhagocytesABSTRACT
Objective@#To explore the changes in polymorphonuclear neutrophils (PMN) function in peripheral blood of patients with sepsis and liver injury and its prognostic value.@*Methods@#A prospective observational study was conducted. The patients who met the criteria of Sepsis-3 admitted to intensive care unit (ICU) of Wuxi People's Hospital Affiliated to Nanjing Medical University from March to August in 2019 were enrolled as the research objects, and the patients were divided into sepsis without liver injury group and sepsis with liver injury group; non-sepsis patients who were hospitalized at the same time were enrolled as non-sepsis group; and the healthy people in the physical examination center were enrolled as healthy control group. The gender, age, white blood cell (WBC), PMN and procalcitonin (PCT) were recorded when the patients were admitted to ICU as well as the people on the day of physical examination. The acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and sequential organ failure assessment (SOFA) scores were calculated. The 28-day mortality was recorded. The quantitative level of neutrophil extracellular traps (NETs) which reflected by circulating free DNA (cf-DNA/NETs) in peripheral plasma was determined by PicoGreen fluorescence quantitative detection; the qualitative level of NETs was detected by immunofluorescence staining. PMN was extracted from the healthy control group, sepsis without liver injury group and sepsis with liver injury group and cultured in vitro, the quantitative level of cf-DNA/NETs in cell supernatant was determined by PicoGreen fluorescence quantitative detection. The patients were divided into two groups according to 28-day outcome of sepsis patients with liver injury. Receiver operating characteristic (ROC) curve was plotted, and the area under ROC curve (AUC) was calculated to analyze the prognostic value of NETs in sepsis patients with liver injury.@*Results@#Finally, 21 sepsis patients without liver injury, 15 sepsis patients with liver injury, 20 with non-sepsis and 20 with healthy examination were enrolled. There was no significant difference in gender or age among the four groups, indicating that the patients in each group were comparable. The levels of cf-DNA/NETs in peripheral blood, WBC and PMN of the sepsis with and without liver injury groups were significantly higher than those of the healthy control group and non-sepsis group, PCT, APACHE Ⅱ score, SOFA score and 28-day mortality were significantly higher than those of the non-sepsis group, and the levels of cf-DNA/NETs in peripheral blood, PCT and 28-day mortality of the sepsis with liver injury group were significantly higher than those of the sepsis without liver injury group [cf-DNA/NETs (μg/L): 481.60±275.86 vs. 169.76±57.05, PCT (μg/L): 11.29 (1.79, 67.10) vs. 1.11 (0.19, 4.09), 28-day mortality: 73.3% (11/15) vs. 38.1% (8/21), all P < 0.05]. The results of PMN in vitro showed that there was no NETs in normal culture of healthy control group, and a small amount of NETs was detected in sepsis with and without liver injury groups. After stimulation of PMN stimulator phorbol-12-myristate-13-acetic acid (PMA), more NETs were produced in neutrophils of three groups compared with normal culture. Quantitative analysis showed that the level of cf-DNA/NETs in cell supernatant of the sepsis with liver injury group was significantly higher than that of the sepsis without liver injury group (μg/L: 1 872.29±258.44 vs. 1 313.55±147.45, P < 0.01). In 15 sepsis patients with liver injury, 4 patients survived for 28 days (26.7%) and 11 died (73.3%). The cf-DNA/NETs level of the dead group on the day of admission was significantly higher than that of the survival group (μg/L: 582.36±160.05 vs. 241.17±96.14, P < 0.05). ROC curve analysis showed that the AUC of NETs level in peripheral blood for predicting 28-day death of sepsis patients with liver injury was 0.932 [95% confidence interval (95%CI) was 0.787-1.000]; when the best cut-off value was 266.81 μg/L, the sensitivity was 90.9%, the specificity was 75.0%, and the approximate index was 0.659.@*Conclusions@#The function of NETs in sepsis patients with liver injury has been further changed. The level of peripheral blood NETs has a certain guiding value for the prognosis of sepsis patients with liver injury.
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To explore the changes in polymorphonuclear neutrophils (PMN) function in peripheral blood of patients with sepsis and liver injury and its prognostic value. Methods A prospective observational study was conducted. The patients who met the criteria of Sepsis-3 admitted to intensive care unit (ICU) of Wuxi People's Hospital Affiliated to Nanjing Medical University from March to August in 2019 were enrolled as the research objects, and the patients were divided into sepsis without liver injury group and sepsis with liver injury group; non-sepsis patients who were hospitalized at the same time were enrolled as non-sepsis group; and the healthy people in the physical examination center were enrolled as healthy control group. The gender, age, white blood cell (WBC), PMN and procalcitonin (PCT) were recorded when the patients were admitted to ICU as well as the people on the day of physical examination. The acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and sequential organ failure assessment (SOFA) scores were calculated. The 28-day mortality was recorded. The quantitative level of neutrophil extracellular traps (NETs) which reflected by circulating free DNA (cf-DNA/NETs) in peripheral plasma was determined by PicoGreen fluorescence quantitative detection; the qualitative level of NETs was detected by immunofluorescence staining. PMN was extracted from the healthy control group, sepsis without liver injury group and sepsis with liver injury group and cultured in vitro, the quantitative level of cf-DNA/NETs in cell supernatant was determined by PicoGreen fluorescence quantitative detection. The patients were divided into two groups according to 28-day outcome of sepsis patients with liver injury. Receiver operating characteristic (ROC) curve was plotted, and the area under ROC curve (AUC) was calculated to analyze the prognostic value of NETs in sepsis patients with liver injury. Results Finally, 21 sepsis patients without liver injury, 15 sepsis patients with liver injury, 20 with non-sepsis and 20 with healthy examination were enrolled. There was no significant difference in gender or age among the four groups, indicating that the patients in each group were comparable. The levels of cf-DNA/NETs in peripheral blood, WBC and PMN of the sepsis with and without liver injury groups were significantly higher than those of the healthy control group and non-sepsis group, PCT, APACHE Ⅱ score, SOFA score and 28-day mortality were significantly higher than those of the non-sepsis group, and the levels of cf-DNA/NETs in peripheral blood, PCT and 28-day mortality of the sepsis with liver injury group were significantly higher than those of the sepsis without liver injury group [cf-DNA/NETs (μg/L): 481.60±275.86 vs. 169.76±57.05, PCT (μg/L): 11.29 (1.79, 67.10) vs. 1.11 (0.19, 4.09), 28-day mortality: 73.3% (11/15) vs. 38.1% (8/21), all P < 0.05]. The results of PMN in vitro showed that there was no NETs in normal culture of healthy control group, and a small amount of NETs was detected in sepsis with and without liver injury groups. After stimulation of PMN stimulator phorbol-12-myristate-13-acetic acid (PMA), more NETs were produced in neutrophils of three groups compared with normal culture. Quantitative analysis showed that the level of cf-DNA/NETs in cell supernatant of the sepsis with liver injury group was significantly higher than that of the sepsis without liver injury group (μg/L: 1 872.29±258.44 vs. 1 313.55±147.45, P < 0.01). In 15 sepsis patients with liver injury, 4 patients survived for 28 days (26.7%) and 11 died (73.3%). The cf-DNA/NETs level of the dead group on the day of admission was significantly higher than that of the survival group (μg/L: 582.36±160.05 vs. 241.17±96.14, P < 0.05). ROC curve analysis showed that the AUC of NETs level in peripheral blood for predicting 28-day death of sepsis patients with liver injury was 0.932 [95% confidence interval (95%CI) was 0.787-1.000]; when the best cut-off value was 266.81 μg/L, the sensitivity was 90.9%, the specificity was 75.0%, and the approximate index was 0.659. Conclusions The function of NETs in sepsis patients with liver injury has been further changed. The level of peripheral blood NETs has a certain guiding value for the prognosis of sepsis patients with liver injury.
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The neutrophils are activated to produce neutrophil extracellular traps (NETs) to capture and destney pathogens, is an important finding of innate immunity. NETs is a double-edged sword, excess or persistent existence of the NETs can delay the wound healing of diabetes food ulcer.
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Objective To explore whether paraquat (PQ) can induce the formation of neutrophil extracellular traps (NETs) in human peripheral blood.Methods Neutrophils were isolated from healthy human peripheral blood,and the cells were identified by hematoxylin-eosin (HE) strain.The cells were treated with different concentrations of PQ [0 (as control),200,400,600,800,1 000 and 1 200 μmol/L],and the cell viability was measured by cell proliferation and CCK-8 cytotoxicity detection kit,and the median lethal concentration of PQ was selected.The cells were treated with the median lethal concentration of PQ (PQ poisoning group),and the untreated cells were served as the control.Immunofluorescence staining was adopted to evaluate NETs formation.PicoGreen dye was used to determine the quantitative content of circulating free DNA.Western Blot was used to determine the expressions of citrullinated histone 3(H3Cit) and myeloperoxidase (MPO) in the supernatant.Results The purity of neutrophils was about 95％ by HE staining.The cells were treated with different concentrations of PQ,and the result showed that the viability of cells was (58 ± 2)％ with 800 μmol/L PQ for treatment.The immunofluorescence showed that there were few expressions of H3Cit and MPO in neutrophils in the control group,and there was no NETs formation,which was composed of DNA,H3Cit and MPO.Compared with the control group,a large amount of NETs was generated from neutrophils stimulated by 800 μmol/L of PQ.Meanwhile,quantitative result showed that the content of cell free DNA in the supernatant was significantly increased in PQ poisoning group as compared with that of control group (μg/L:2 235 ± 462 vs.561 ± 87,P ＜ 0.01).The protein expressions of H3Cit and MPO in the supernatant were also significantly increased as compared with those of control group [H3Cit protein expression (gray value):0.23 ± 0.03 vs.0.11 ± 0.01,MPO protein expression (gray value):0.47 ± 0.05 vs.0.21 ± 0.04,both P ＜ 0.05].Conclusion 800 μmol/L of PQ can induce the formation of NETs in human peripheral blood.
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Objective To correlate the neutrophil extracellular trap (NET) mitochondrial DNA (mtDNA) and anti-mtDNA antibodies (Abs) with disease activity and clinical features in systemic lupus erythematosus (SLE) patients.Methods We enrolled 102 SLE patients,rheumatoid arthritis (RA) patients (n=30) and healthy donors as controls (n=40).NET were generated from phorbol 12-myristate 13-acetate (PMA)-stimulated peripheral neutrophils.mtDNA levels and the transcriptional levels of five interferon inducible genes(IFIGs)(OAS-1,Mx-1,Ly6e,IFIT1 and IFIT4) were measured by quantitative PCR.Interferon scores (IFN scores) were calculated.Anti-mtDNA Abs were detected by enzyme-linked immunosorbent assay.Spearman's correlation analysis,t test andx2 test were used for statistical analysis.Results mtDNA release by netting neutrophils was greatly enhanced in SLE patients (1 088 000 ±1 133 000) compared with healthy controls (465 900±447 200)(t=2.617,P＜0.01) and significantly correlated with IFN scores (r=0.460 6,P＜0.01).NETs mtDNA in moderate active group (728 300±1 003 000) and severe active group (1 093 000±946 500) were significantly higher than the mild active group (159 500±155 100) (t=2.240,P＜0.05,t=3.894,P＜0.01).Forty-one percent of SLE patients were positive for anti-mtDNA Abs(1.28±0.68),while none of the healthy donors (0.70±0.31) (P＜0.01) and RA controls (0.59±0.18)(P＜0.01) displayed a positive serology response to mtDNA.Addition-ally,the titers of anti-mtDNA Abs were also associated with IFN scores (r=0.292 8,P＜0.05).Anti-mtDNA Abs in moderate active group (1.3±-0.6) and severe active group(1.4±0.7)were significantly higher than the mild active group (0.7±0.4) (t=3.154,3.538,all P＜0.01).The levels of anti-mtDNA Abs significantly correlated with classic an-ti-dsDNA Abs titers measured by Farr assay (r=0.542 9,P＜0.001) and were associated with LN (x2=8.644,P＜0.01).Conclusion mtDNA in NET and anti-mtDNA Abs serve as new biomarkers for disease activity and renal involvement in SLE patients.
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Neutrophils are the most abundant white blood cells in the peripheral blood and have long been recognized as the major phagocytes in acute infection by destroying extracellular pathogens. Although research on neutrophils hampered by intractability in the experiments, the newly discovered effector functions of neutrophils includes granular proteins, and cytokines, extracellular traps. With all effector mechanism neutrophils play a critical role in the pathogenesis of acute and chronic infection, autoimmunity and cancer.