Analysis of CSF1R gene mutation in a Chinese family with hereditary diffuse leukoencephalopathy with neuroaxonal spheroids / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify potential mutation of the colony stimulating factor 1 receptor gene (CSF1R) in a large Chinese family affected with hereditary diffuse leukoencephalopathy with spheroids (HDLS) and analyze the genotype-phenotype correlation.</p><p><b>METHODS</b>The proband was evaluated physically and radiologically to ascertain the HDLS phenotype. Genomic DNA was extracted from peripheral blood samples from family members. The coding region of the CSF1R gene was amplified with PCR and subjected to direct DNA sequencing.</p><p><b>RESULTS</b>There were 9 affected members (5 alive) in this five-generation family (1 member had died during the follow-up). A missense mutation c.2563C>A (p.P855T) of the CSF1R gene has been identified in the proband. The same mutation was identified in 3 affected and 1 unaffected members of the family.</p><p><b>CONCLUSION</b>The family was consistent with autosomal dominant inheritance. CSF1R gene mutation is also a disease-causing mutation in Chinese patients.</p>

Serum amyloid A inhibits RANKL-induced osteoclast formation

When mouse bone marrow-derived macrophages were stimulated with serum amyloid A (SAA), which is a major acute-phase protein, there was strong inhibition of osteoclast formation induced by the receptor activator of nuclear factor kappaB ligand. SAA not only markedly blocked the expression of several osteoclast-associated genes (TNF receptor-associated factor 6 and osteoclast-associated receptor) but also strongly induced the expression of negative regulators (MafB and interferon regulatory factor 8). Moreover, SAA decreased c-fms expression on the cell surface via shedding of the c-fms extracellular domain. SAA also restrained the fusion of osteoclast precursors by blocking intracellular ATP release. This inhibitory response of SAA is not mediated by the well-known SAA receptors (formyl peptide receptor 2, Toll-like receptor 2 (TLR2) or TLR4). These findings provide insight into a novel inhibitory role of SAA in osteoclastogenesis and suggest that SAA is an important endogenous modulator that regulates bone homeostasis.

The expressional alterations of CSF-1R after ischemic injury of cerebral cortex / 中国应用生理学杂志

<p><b>AIM</b>To observe the expressional alterations of colony stimulating factor-1 receptor (CSF-1R) after ischemic injury of cerebral cortex, and study the function of colony stimulating factor-1 (CSF-1)/CSF-1R signal during the process of ischemic injury and repair of central nervous system (CNS).</p><p><b>METHODS</b>We examined the distribution and expression of CSF-1R in normal brain tissues and ischemic brain tissues by immunohistology and Western blot analysis.</p><p><b>RESULTS</b>The expression of CSF-1R in neurons could be up-regulated by ischemic injury in CNS.</p><p><b>CONCLUSION</b>CSF-1/CSF-1R might take part in the process of ischemic injury and repair.</p>

Effects of soluble M-CSF receptor on differentiation of umbilical cord blood-derived myelomonocytic hematopoietic precursors in mesenchymal stem cell microenvironment / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the effects of soluble M-CSF receptor (sMR) on proliferation and differentiation of hematopoietic precursors derived from umbilical cord blood in mesenchymal stem cell (MSC) microenvironment.</p><p><b>METHOD</b>In group of cytokine (CK) + sMR, MSCs were used as feeder cells, mononuclear cells (MNCs) from cord blood were expanded in MSC microenvironment in presence of SCF, Flt3L, TPO, IL-6 and sMR. In CK control group, no sMR was added. MNC counting and colony forming cell (CFC) culture were performed at week 1, 2, 3 and 4.</p><p><b>RESULTS</b>1) The number of MNCs increased rapidly in both group CK and group CK + sMR (108.47 -fold and 120.67 -fold, respectively, P > 0.05). 2) CFC increased, peaked at week 3(38.1 x 10(3)) and declined rapidly at week 4(18.1 x 10(3)) in group CK, but still increased in group CK + sMR at week 4 (84 x 10(3)), the total number of CFC was higher in group CK + sMR than in group CK at week 3 and week 4 (P <0.01). 3) The erythroid CFC peaked at week 1 (5891.2 and 5635.6 for groups CK and CK + sMR, respectively), then dropped rapidly and to zero at week 3, in both group CK and group CK + sMR (P > 0. 05). 4) Myeloid CFC expanded continuously and peaked at week 3 (31.5 x 10(3)), then declined at week 4 (18.3 x 10(3)) in group CK; but still increased at week 4(80.8 x 10(3)) in group CK + sMR, being higher than that in group CK at week 3 and week 4 (P <0.01).</p><p><b>CONCLUSION</b>sMR can inhibit the differentiation of cord blood hematopoietic precursors expanded in MSC microenvironment, but the inhibition exerts only on myelomonocytic but not on erythroid precursors.</p>

Clinical characteristics and immunophenotype of aged patients with acute leukemia / 中国实验血液学杂志

In order to analyze the clinical characteristics and biological features of acute leukemia in elderly, 104 acute leukemia patients in elderly were retrospectively analyzed and compared with 71 acute leukemia patients below 60 years old. The results showed that: (1) the proportion of AML in the aged group (73%) was higher than that in the young group (54.9%), and the difference was statistically significant (P < 0.05), but AML (M3) was absent in the aged group; (2) the median of bone marrow blast cell in the aged group was significantly lower than that in the young group (P < 0.05); (3) in AML, the frequently of CD14 expression was higher in the aged group (18.8%) than that in the young group (2.6%), while the expression frequencies of CD15 (37.5%), CD117 (62.5%), and CD38 (59.4%) were respectively lower in the aged group than that in the young group which were (69.2%) for CD15, (89.7%) for CD17, and (84.6%) for CD38 respectively, and the difference was also statistically significant (P < 0.05). (4) CD19 was most frequently expressed in ALL of the aged group and the positive rate was 100%; (5) there was no significant difference in expression of special lineage antigens and overlapping lineage antigens between the aged group and the young group (P > 0.05); (6) the expression frequency of unfavorable karyotypes in the aged group was higher than that in the young group, and the difference was statistically very significant (P < 0.01); (7) the complete remission rate (CR rate) in the aged group was 42.9%, 2-year survival rate in the aged group was 5.4%, and treatment-related mortality rate in the aged group was 26.8%, while the CR rate in the young group was 76.6%, the difference was statistically significant (P < 0.05). It is concluded that the expression frequency of CD14 associated with unfavorable prognosis is higher in the aged group than that in the young group, while the expression frequency of CD15 associated with favorable prognosis is lower in the aged group than that in the young group. The expression frequency of unfavorable karyotypes in the aged group is higher than that in the young group. The CR rate of acute leukemia in elderly is low, thus the patients in elderly often have unfavorable prognosis.

Cardiac valve MCSF-1 and its receptor expression changes in Staphylococcus aureus induced infective endocarditis / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the cellular immunology mechanism of infective endocarditis (IE), we investigated the effects of Staphylococcus aureus (S. aureus) on MCSF-1 and its receptor (c-fms) gene expression in cardiac valves.</p><p><b>METHODS</b>Thirty-two rabbits were divided into 4 groups: mitral or tricuspid valve artificial lesions with 5 x 10(4) CFU or 5 x 10(6) CFU S. aureus injection. Control rabbits (n = 7) received 5 x 10(6) CFU S. aureus injection. IE after operation were confirmed by naked eyes and electron microscope observations. MCSF-1, c-fms in mitral and tricuspid valves were detected by RT-PCR.</p><p><b>RESULTS</b>Twenty-six rabbits survived the operation and 14 rabbits developed IE (2 with 5 x 10(4) CFU and 12 with 5 x 10(6) CFU S. aureus injection) one day post operation. S. aureus injection alone did not induce IE. Compared to control rabbits, MCSF-1 mRNA was significantly upregulated and c-fms mRNA significantly downregulated after 5 x 10(4) CFU S. aureus injection with heart valve artificial lesion in mitral valves or tricuspid valves. MCSF-1 expression in mitral valves was further increased while remained unchanged in tricuspid valve after 5 x 10(6) CFU S. aureus injection compared to that in 5 x 10(4) CFU S. aureus injection group.</p><p><b>CONCLUSION</b>High dose bacterial invasion and heart valves lesion were the main factors for inducing infective endocarditis. Development of infective endocarditis was associated with valve MCSF-1/c-fms expression changes in this rabbit model.</p>

The effects of different transcripts of AML1 on the transactivation of M-CSF-R gene / 中华血液学杂志

<p><b>OBJECTIVE</b>To observe the effects of AML1A and AML1B, two splicing isoforms of AML1, on the transactivation of macrophage colony-stimulating factor receptor (M-CSF-R), and explore the mechanism of hematopoietic stem cell committed differentiation and leukemogenesis.</p><p><b>METHODS</b>The expressive plasmids of AML1A and AML1B were constructed, and co-transfected into CV-1 cells with a luciferase reporter plasmid containing M-CSF-R promoter. The transactivity of M-CSF-R promoter was assayed by luminometer.</p><p><b>RESULTS</b>AML1B exhibited a distinct transactivity to M-CSF-R promoter with a sequence-specificity and dosage-dependent manner. AML1A showed no any transactivity but antagonized the effect of AML1B, causing marked reduction of M-CSF-R expression.</p><p><b>CONCLUSION</b>An intact structure of AML1 is necessary for transactivation of M-CSF-R. AML1A may interfere with the transactivation of AML1B, and play a key role in the fine regulation of committed differentiation of hematopoietic cell.</p>

Colony-stimulating factor-1 receptor in rat dental follicle cells / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To study localization and expression of CSF-1 receptor protein, in order to discover the CSF-1 and IL-1alpha effects on CSF-1 receptor mRNA levels and to determine if the autocrine effect is inhibited through the CSF-1 receptor.</p><p><b>METHODS</b>Immunolocalization of CSF-1 receptor in the cultured dental follicle cells and in mandibles of the post-natal rats from day 1 to 11 were performed. The effects of different concentrations of CSF-1, IL-1alpha on CSF-1 receptor gene expression were detected by means of RT-PCR.</p><p><b>RESULTS</b>Cultured dental follicle cells were immunostained for the CSF-1 receptor. In vivo, immunostaining showed that the CSF-1 receptor was present in the dental follicle of the first mandibular molar at early post-natally and was either absent or greatly reduced by day 11 post-natally. High concentrations of cvCSF-1 reduced the gene expression of the CSF-1 receptor. IL-1alpha had no effects on CSF-1 receptor mRNA levels.</p><p><b>CONCLUSIONS</b>The expression of CSF-1 receptor reaches a peak early post-natally in the dental follicle of the first mandibular molar of the rat and then subsequently declines. High concentrations of CSF-1 inhibits the expression of CSF-1 receptor, IL-1alpha has no effect on the expression of CSF-1 receptor mRNA.</p>

The expression, characterization and roles of macrophage colony-stimulating factor receptor in human leukemia cell lines / 中华病理学杂志

<p><b>OBJECTIVE</b>To explore the expression, characteristics and roles of macrophage colony-stimulating factor receptor (M-CSF-R) in human leukemia cell lines.</p><p><b>METHODS</b>Peripheral blood mononuclear cells (PBMCs) collected from 3 healthy persons, cord blood mononuclear cells (CBMCs) collected from 5 healthy persons and 4 human myelomonocytic leukemia cell lines including J6-1, J6-2, K562 and HL-60 were studied by using ABC immunoperoxidaes assay, indirect immunofluorescene staining, flow cytometry, and Western blot.</p><p><b>RESULTS</b>M-CSF-R was noticed to be localized in the cytoplasm, nucleus and at the membrane in 4 human leukemia cell lines; expression of M-CSF-R was not detected in normal human PBMCs without PHA stimulation. Human PBMCs stimulated by PHA expressed a low level of M-CSF-R. Frequencies of membrane bound M-CSF-R (M-CSF-mR) expression in J6-1, J6-2, K562 and HL-60 were 78.9%, 72.6%, 54.9% and 58.0% respectively. Frequencies of cytoplasm and nucleus associated M-CSF-R (M-CSF-cnR) were 52.3%, 44.3%, 28.0% and 65.3% respectively. One form of M-CSF-R with a molecular weight of 120 000 was detected both in the cytoplasm and nucleus of HL-60 cells. The half-life of M-CSF-cnR in leukemia cells mentioned above was longer than that of corresponding M-CSF-R in stimulated CBMCs, and the half-life of M-CSF-mR in leukemia cells was extended except that of M-CSF-mR in K562 cells. Both anti-M-CSF-R monoclonal antibody and recombinant human M-CSF soluble receptor could cause the growth arrest of HL-60 cell in G(0)/G(1) phase, and could inhibit the formation of colony of HL-60 cell in soft agarose.</p><p><b>CONCLUSIONS</b>Expression of M-CSF-R in leukemia cells is heterogeneous. The accumulation of cellular M-CSF-R results in the low degradation rate of cellular M-CSF-R in leukemia cells, which could be a potential mitotic signal. Signal mediated by M-CSF-R is important and necessary for the growth of HL-60 cell.</p>