UNIPROT:P04141 - FACTA Search

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Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human polymorphonuclear leukocytes (PMN) preincubated overnight with 100 U/mL gamma-interferon (IFN-gamma) had an increased metabolic response, as measured by iodination and/or superoxide production, to stimulation by tumor necrosis factor (TNF), granulocyte-macrophage colony-stimulating factor (GM-CSF), formylmethionyl-leucyl-phenylalanine (FMLP), opsonized zymosan, and lipopolysaccharide (LPS), as compared with cells comparably preincubated in the absence of IFN-gamma. The decline in the staphylocidal activity of the stored PMN was also prevented in part by IFN-gamma, as was the depressed adherence of PMN stimulated with phorbol myristate acetate (PMA), FMLP, TNF, GM-CSF, and LPS. This protective effect of IFN-gamma on PMN function was associated with the prolonged surface expression of the complement receptor three (CR3) alpha-chain (CD11b), CR3 beta-chain (CD18), FcRII (CD32), and FcRIII (CD16), and the appearance of surface FcRI (CD64). The polymerase chain reaction (PCR) was used to amplify neutrophil RNA-derived cDNA recognized by synthetic oliogonucleotides designed from published nucleotide sequences for specific proteins. Using this procedure, mRNA for gp91-phox, p67-phox, p47-phox, CD64, two forms of CD32, CD16, CD11b, CD18, and actin were found to be depressed after overnight storage of neutrophils, and this decrease in steady-state mRNA levels was in part or totally prevented by IFN-gamma. CD64 and gp91-phox mRNA were generally increased by IFN-gamma to a level greater than that of freshly isolated neutrophils. Northern analysis of CD64 and p47 phox mRNAs confirmed the findings with the PCR method. These findings suggest that storage of PMN in a functionally active state is favored by the presence of IFN-gamma.
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PMID:Effects of gamma-interferon on human neutrophils: protection from deterioration on storage. 131 36

Using an in vitro expansion and differentiation system for human CD34+ cord blood (CB) progenitor cells, we analyzed the induction and expression kinetics of the granulomonocyte associated lysosomal proteins myeloperoxidase (MPO), lysozyme (LZ), lactoferrin (LF), and macrosialin (CD68). Freshly isolated CD34+ CB cells were negative for LZ and LF, and only small proportions expressed MPO (4% +/- 2%) or CD68 (3% +/- 1%). Culturing of CD34+ cells for 14 days with interleukin (IL)-1, IL-3, IL-6, stem cell factor, granulocyte-macrophage colony-stimulating factor (GM-CSF), and G-CSF resulted in on average a 1,750-fold amplification of cell number, of which 83% +/- 7% were MPO+. Without addition of GM-CSF and G-CSF, lower increases in total cell numbers (mean, 211-fold) and lower proportions of MPO+ cells (54% +/- 11%) were observed. The proportion of MPO+ cells slightly exceeded but clearly correlated with the proportion of cells positive for the granulomonocyte associated surface molecules CD11b (Mac-1), CD15 (LeX), CD64 (Fc gamma RI) CD66, or CD89 (Fc alpha R). At day 14 MPO+ and LZ+ cells were virtually identical. However, at earlier time points during culture (days 4 and 7), single MPO+ or LZ+ cell populations were also observed, which only later acquired LZ and MPO, respectively. Maturation of cells into the neutrophilic pathway was indicated by the acquisition of MPO, followed by LZ. In contrast, maturation of cells into the monocytic pathway was indicated by the acquisition of LZ followed by MPO and CD14. CD68 was found to be expressed at day 4 by the majority of cells and was not restricted to the granulomonocytic cells, as cells with megakariocytic (CD41+) or erythroid (CD71hi) features were CD68+. LF expression was observed only in GM- plus G-CSF-supplemented cultures, in which only 26% +/- 5% of cells expressed LF by day 14.
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PMID:Granulomonocyte-associated lysosomal protein expression during in vitro expansion and differentiation of CD34+ hematopoietic progenitor cells. 749 68

The aim of this study was to identify markers specific for granulo-monocytic commitment of progenitor cells. Large panels of antibodies were screened for selective staining of subsets of CD34+ cells from fetal and adult bone marrow. Flow cytometric analysis showed that CD64/fc gamma RI was undetectable on noncommitted progenitor cells (CD34++, CD38-/lo, HLA-DR+) and expressed on a subset of lineage-committed progenitors (CD34+, CD38+) with higher mean orthogonal light scatter than the remaining CD34+ cells. The CD34+, CD64+ cells were CD19- and the majority were CD45RA+, CD71lo, suggesting that CD64 recognized granulomonocytic progenitor cells. Specificity of CD64 for the granulo-monocytic lineage was shown by demonstrating that colonies arising from CD34+, CD64+ cells consisted of 98% +/- 2% colony-forming unit-granulocyte-macrophage (CFU-GM) in semisolid medium containing stem cell factor (SCF), interleukin-3 (IL-3), IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), and erythropoietin (EPO). In contrast, 63% +/- 15% of the colonies from the CD34+, CD64- cells were burst-forming unit-erythroid/colony-forming unit-erythroid (BFU-E/CFU-E). Furthermore, four-color immunofluourescence and cell sorting was used to analyze the progeny of cells cultured in liquid medium containing identical cytokines as used in the semisolid medium. This analysis showed that CD34+, CD64+ cells gave rise to 83% +/- 10% granulo-monocytic cells whereas progeny of the CD34+, CD64- cells contained 81% +/- 11% erythroid cells. Neutrophils as well as basophils and monocytes/macrophages were present in the cultures from CD34+, CD64+ cells, showing that this population contains progenitors of most types of granulo-monocytic cells. Two widely used myeloid markers, CD13 and CD33, were not myeloid-specific, because both were clearly positive on noncommitted progenitor cells. Of 40 antigens tested, CD15 was the only other marker fulfilling the criteria of a myeloid-specific marker. However, at concentrations of CD15 that did not induce aggregation, CD15+ cells constituted less than 50% of the CD34+, CD64+ cells. Furthermore, the CD34+, CD15- cells showed more than 50% higher CD34 mean fluorescence intensity than the CD64+, CD15+ cells, indicating that CD64 appears earlier than CD15 during differentiation. Thus, among a large number of antigens screened, CD64 was the most useful for the identification and purification of granulo-monocytic progenitor cells.
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PMID:CD64/Fc gamma RI is a granulo-monocytic lineage marker on CD34+ hematopoietic progenitor cells. 753 12

The effects of 1 alpha,25-dihydroxyvitamin D3/calcitriol on the expression of Fc receptors (FcR) for IgA (Fc alpha R), IgE (Fc epsilon RII), and IgG (Fc gamma R) on human peripheral blood monocytes and the cell lines U937, THP-1, and Mono Mac-6, in combination with various cytokines, was examined by flow cytometry. On both monocyte-derived macrophages and the myelomonocytic cell lines, Fc alpha R/CD89 expression was induced by calcitriol alone and additively in combination with tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and granulocyte-macrophage colony-stimulating factor. Constitutive and interleukin-4 (IL-4)-driven Fc epsilon RII/CD23 expression was markedly diminished on calcitriol-treated U937 cells and monocytes. Fc epsilon RII was also triggered by IFN-gamma, TNF-alpha, and IL-6 on all the cell lines, an effect blocked by calcitriol. On monocytes, the basal level and IFN-gamma-induced Fc gamma RI/CD64 expression was down-regulated by calcitriol and IL-4. The expression of Fc gamma RII/CD32 on monocytes was strongly suppressed by calcitriol. Transforming growth factor-beta induced Fc gamma RIII/CD16 on monocytes, an effect opposed by calcitriol. The ability of calcitriol-treated monocytes to phagocytose IgG-sensitized ox erythrocytes was diminished. Our results demonstrate that calcitriol, alone or in combination with cytokines, modulates Fc alpha R, Fc epsilon RII, Fc gamma RI, and Fc gamma RII expression on human mononuclear phagocytes, as well as Fc gamma R-mediated phagocytosis.
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PMID:Modulation of IgA, IgE, and IgG Fc receptor expression on human mononuclear phagocytes by 1 alpha,25-dihydroxyvitamin D3 and cytokines. 764 18

We have previously shown that tumor necrosis factor (TNF)alpha strongly potentiates the granulocyte-macrophage colony-stimulating factor (GM-CSF)/interleukin (IL)-3-dependent proliferation of CD34+ hematopoietic progenitor cells (HPC) through the recruitment of early progenitors with high proliferative potential. Furthermore, the combination of GM-CSF and TNFalpha allows the generation of large numbers of dendritic/Langerhans cells (D-Lc). Herein, we analyzed whether IL-3, when combined to TNFalpha would, as does GM-CSF, allow the generation of CD1a+ D-Lc. Accordingly, cultures of cord blood CD34+ HPC with IL-3 + TNFalpha yielded 20% to 60% CD14+ cells and 11% to 17% CD1a+ cells, while IL-3 alone did not generate significant numbers of CD1a+ cells. Although the percentage of CD1a+ cells detected in IL3 + TNFalpha was lower than that observed in GM-CSF + TNFalpha (42% to 78%), the strong growth induced by IL-3 + TNFalpha generated as many CD1a+ cells as did GM-CSF + TNFalpha. The CD14+ and CD1a+ cells generated with IL-3 + TNFalpha are similar to CD14+ and CD1a+ cells generated in GM-CSF alone and GM-CSF + TNFalpha, respectively. CD1a+ cells differed from CD14+ cells by (1) dendritic morphology, (2) higher expression of CD1a, CD1c, CD4, CD40, adhesion molecules (CD11c, CD54, CD58), major histocompatibility complex (MHC) class II molecules and CD28 ligands (CD80 and CD86), (3) lack of Fc receptor FcgammaRI (CD64) and complement receptor CR1 (CD35) expression, and (4) stronger induction of allogeneic T-cell proliferation. Thus, in combination with TNFalpha, IL-3 is as potent as GM-CSF for the generation of CD1a+ D-Lc from cord blood CD34+ HPC. The dendritic cell inducing ability of IL-3 may explain why mice with inactivated GM-CSF gene display dendritic cells.
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PMID:Interleukin-3 cooperates with tumor necrosis factor alpha for the development of human dendritic/Langerhans cells from cord blood CD34+ hematopoietic progenitor cells. 863 Apr 1

Culturing human monocytes in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) has been reported to provoke the formation of multinucleated giant cells (GCs). In the present work, GCs were generated in a two-step procedure in which macrophages were first differentiated from monocytes before being fused into GCs. The two cytokines used acted sequentially. GM-CSF was required for monocyte differentiation and IL-4 for macrophage fusion. Macrophages were purified from cultures of blood mononuclear cells maintained for 7 days in plastic bags. When seeded in conventional plastic-ware in the presence of IL-4, these macrophages showed an increased motility, spread in thin cytoplasmic lamellas, regrouped in clusters, and within 1-3 weeks, differentiated into GCs. Multinucleated cells also appeared in IL-4-untreated macrophage cultures but the number of nuclei did not exceed 2 or 3, compared with more than 30 in the presence of IL-4. Scanning electron microscopy of GCs showed highly developed pseudopods. GCs reacted with anti-CD11b, -CD54, -CD68, -HLA-ABC, and -HLA-DR monoclonal antibodies and AMH-152 but were CD14- and CD64-negative. Both untreated and IL-4-treated macrophages conserved pinocytic and phagocytic activity. Thus, IL-4 induced a differentiation process in which macrophages lost markers like CD14 and CD64, acquired an enhanced membrane motility, and fused in multinucleated GCs.
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PMID:Generation of multinucleated giant cells by culture of monocyte-derived macrophages with IL-4. 910 39

Treatment of human polymorphonuclear leucocytes (PMNL) separated by density sedimentation (DS) from normal donors (PMNL-NL-DS) with interferon-gamma (IFN-gamma) + granulocyte colony-stimulating factor (G-CSF) lessens the damage caused by isolation and irradiation. We have studied granulocyte-macrophage colony-stimulating factor (GM-CSF) in this system, as well as the behaviour of PMNL collected by continuous flow leucapheresis (CFL) from donors treated with G-CSF (PMNL-GCSF-CFL). After isolation, PMNLs were treated with IFN-gamma + G-CSF, GM-CSF or IFN-gamma + G-CSF + GM-CSF, irradiated with 0 or 30 Gy and studied after 0 and 20 h in cell culture. All regimens reduced apoptosis of PMNL-NL-DS. Killing of Candida albicans by 20-h-old PMNL-NL-DS was best preserved by IFN-gamma + G-CSF treatment. A similar pattern of results was obtained for assays of PMNL-NL-DS chemotaxis and superoxide production. There was a consistent trend toward reduced function after irradiation in all assays. PMNL-GCSF-CFL less often demonstrated the morphological features of apoptosis, and this was further reduced by cytokine regimens containing IFN-gamma + G-CSF. In assays of C. albicans killing and chemotaxis, 20-h-old untreated PMNL-GCSF-CFL performed as well as freshly isolated PMNL-GCSF-CFL. PMNL-GCSF-CFL showed decay in CD11b (CR3), CD16 (Fc gamma III) and CD64 (Fc gamma R1) expression after 20 h in cell culture, but treatment with IFN-gamma + G-CSF preserved expression. There was a trend toward reduced function after radiation. Comparison of PMNL-GCSF separated by CFL and DS demonstrated that CFL itself is a strong inducer of the morphological features of apoptosis. This study shows that while separation by CFL, and irradiation are damaging to PMNLs, damage may be reduced by use of cytokines.
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PMID:Effects of in vitro and in vivo cytokine treatment, leucapheresis and irradiation on the function of human neutrophils: implications for white blood cell transfusion therapy. 914 46

Recent experimental data have shown that mice could be immunized efficiently, in particular against cancer, by the injection of antigen-loaded dendritic cells (DC) or macrophages (MPH). In the present work, these two antigen-presenting cells (APC) were prepared in humans from circulating mononuclear cells (MNC). MPH were obtained from MNC that were cultured in hydrophobic plastic bags and purified by elutriation. DC were from the culture of adherent elutriation-purified monocytes in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). The two APC were prepared in parallel from the same donors and their phenotype and antigen-presenting capacity were compared. DC differed from MPH by a higher expression of HLA-DR and CD23 and a lower expression of CD14, CD64 and of adhesion molecules. DC and MPH were comparably effective in (a) enhancing the mitotic response of autologous lymphocytes to immobilized anti-CD3 (accessory function); (b) presenting melanoma peptides to specific cytotoxic T lymphocyte (CTL) clones; and (c) stimulating the generation of CTL directed against a myxovirus influenza peptide. However, DC were more effective than MPH in inducing the mitotic response of allogeneic peripheral blood leucocytes (PBL), possibly because of their higher expression of HLA class II molecules. In conclusion, DC and MPH prepared from blood MNC did not differ substantially in their ability to activate HLA class I-restricted T-cell responses by exogenous peptide presentation.
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PMID:Human monocyte-derived macrophages and dendritic cells are comparably effective in vitro in presenting HLA class I-restricted exogenous peptides. 937 6

There is increasing interest in the role of blood polymorphonuclear leukocytes (PMNs) in the pathogenesis of sickle cell crisis. We studied the adherence of PMNs from 18 sickle cell patients in crisis, 25 out of crisis, and 43 healthy subjects (controls) to monolayers of human umbilical cord endothelium that were either untreated or pretreated with tumor necrosis factor alpha (TNFalpha). Overall, the PMNs from patients in crisis were more adherent than control PMNs to untreated endothelial monolayers (mean 53% increase; P < .001) and TNFalpha-treated monolayers (mean 41% increase; P < .002). Increased adhesiveness was not associated with an abnormal expression of CD11a, CD11b, CD11c, CD18, CD62L, or CD15. There was an increase in the number of PMNs expressing CD64 in patients in crisis (median value, 44%) compared with patients out of crisis (median, 21%; P = .025) and controls (median, 6.5%; P < .001). Sera from patients in crisis had normal levels of granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interferon-gamma, TNFalpha, interleukin-1 (IL-1), IL-6, or IL-8 and did not modify the adherence of PMNs or their expression of CD64. Only IFN-gamma induced CD64 expression on PMNs, but this effect was not associated with enhanced binding to endothelium. Because PMNs bound to endothelial monolayers were CD64(+) and CD64-enriched PMNs were 7 times more adherent to endothelial monolayers than CD64-depleted PMNs, it is likely that CD64 is a marker of adherent PMNs. Two of the three anti-CD64 antibodies used in our antibody blocking studies (clones 32.2 and 197) partially inhibited the binding of sickle cell PMNs to untreated endothelium (mean inhibitions of 33% [P = .01] and 21% [P = .03], respectively), whereas only one (clone 197) inhibited binding to TNFalpha-treated endothelium (mean inhibition, 29%; P = . 004). In some patients with sickle cell disease, an enhanced PMN adhesion to vascular endothelium could contribute to the vascular occlusion that characterizes the acute crisis of the disease.
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PMID:Blood polymorphonuclear leukocytes from the majority of sickle cell patients in the crisis phase of the disease show enhanced adhesion to vascular endothelium and increased expression of CD64. 941 94

Granulocyte-macrophage colony-stimulating factor (GM-CSF) (250 microg/m2) was administered subcutaneously to 7 normal volunteers for up to 14 days to study its effects on neutrophil kinetics and function. With treatment, blood neutrophil counts rose gradually to peak at 3 1/2 times baseline by day 14. At day 5 marrow mitotic cells were increased and post-mitotic cells decreased, and the transit time through the post-mitotic marrow pool accelerated (normal = 6.4 days, GM-CSF = 3.9 days; P < 0.01). Treatment had little effect on the blood neutrophil half-life (normal = 9.6 +/- 1.3 hours; GM-CSF = 13.1 +/- 2.4 hours, P > 0.05); or the neutrophil turnover rate (normal = 78.5 +/- 11.9 x 10(7)/cells/kg/day, GM-CSF = 91.4 +/- 19.8 x 10(7)/cells/kg/day, P > 0.05). GM-CSF reduced the number of neutrophils migrating to skin chambers (normal = 104 +/- 25.0 x 10(6)/cells, GM-CSF = 48.6 +/- 16.0 x 10(6)/cells; P < 0.05). Treatment increased expression of CD11b/CD18 but not Fcgamma receptors (CD16, CD32, CD64). Treatment also stimulated the in vitro neutrophil respiratory burst in response to a variety of agonists, and this enhancement persisted for the duration of treatment. All subjects experienced local and systemic adverse effects and developed eosinophilia. This study indicates that GM-CSF at a dose of 250 microg/m2 causes neutrophilia chiefly by accelerating delivery of neutrophils from the marrow to the blood and by decreasing migration from the blood to the tissues, with only a modest effect on neutrophil production and blood half-life.
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PMID:Effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) on neutrophil kinetics and function in normal human volunteers. 942 10

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