Gene/Protein Disease Symptom Drug Enzyme Compound
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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)

L-selectin (LECAM-1, LAM-1, MEL-14 antigen, Dreg antigen) is one of the molecules controlling lymphocyte homing from the blood to peripheral lymph nodes and granulocyte adhesion to inflamed endothelium. In this work, regulation of L-selectin expression on mouse bone marrow cells was studied. L-selectin-negative cells were isolated by panning technique, cultured for 1-7 days with cytokines and mitogens, and L-selectin expression was analyzed by immunofluorescence staining. When cultured for 3 days with interleukin (IL) 1, IL 2, IL 5, IL 6, phytohemagglutinin, pokeweed mitogen or in the medium alone, 75%-85% of L-selectin-negative large cells (including granulocytes, macrophages/monocytes, blasts and their precursors) became L-selectin positive. In contrast, IL 3, IL 4, granulocyte-macrophage colony-stimulating factor (GM-CSF) and lipopolysaccharide (LPS) prevented the induction of L-selectin in a time- and dose-dependent manner. GM-CSF was the most potent inhibitor and only 10%-15% of cells became L-selectin positive after 3 days of culture. Furthermore, L-selectin was down-regulated on cultured unselected bone marrow cells by IL 3, IL 4, GM-CSF and LPS stimulation. After culture, the relative molecular mass of L-selectin was 100 kDa, similar to the size of the granulocyte form of this antigen. Cultured cells adhered to high endothelial venules (HEV) only 10%-32% as effectively as freshly isolated bone marrow cells despite high levels of L-selectin expression. The phenotypic analysis and the HEV binding data indicate that after culturing L-selectin was almost exclusively expressed on bone marrow leukocytes of myeloid series, and on these cells it was not functional in mediating peripheral lymph node HEV binding. Overall, these results show that the expression of L-selectin can be modulated by regulating the maturation and differentiation of the cells in vitro. This supports the idea that different cytokines and mitogens may also be important in controlling migrational status of leukocytes in vivo.
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PMID:Regulation of L-selectin expression on cultured bone marrow leukocytes and their precursors. 137 61

Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) are frequently used in the clinical management of neutropenia. These cytokines not only enhance the proliferation of myeloid precursor cells but also influence the function of mature leukocytes. In a previous study, we found that the in vivo effects of G-CSF on neutrophils differed from those in vitro. In the present study, we investigated the effects of a single dose of recombinant GM-CSF (7.5 microg/kg, subcutaneously) on neutrophils, eosinophils, and monocytes in healthy volunteers. We analyzed leukocyte kinetics, phenotypical changes, neutrophil degranulation, and systemic cytokine production. After GM-CSF injection, phenotypical changes included upregulation of CD11b on all three cell types and a decreased expression of L-selectin and Fc(gamma)RIII on neutrophils. Neutrophil degranulation was evident from the increased plasma concentrations of lactoferrin and elastase. GM-CSF induced the release of interleukin-8 (IL-8), but not of IL-6 or tumor necrosis factor alpha. In comparison to the results from our previous study with G-CSF in healthy volunteers, GM-CSF induced a stronger activation of mature neutrophils but had a much less pronounced effect on the production and maturation of neutrophil precursors. These data may help to guide the choice between the two cytokines in different clinical situations.
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PMID:A single dose of granulocyte-macrophage colony-stimulating factor induces systemic interleukin-8 release and neutrophil activation in healthy volunteers. 865 46

We have previously shown that surface levels of the adhesive glycoprotein, L-selectin, are diminished on cord blood neutrophils (polymorphonuclear leukocytes, PMN) and associated with impaired adherence to endothelium under flow conditions. To test the hypothesis that diminished surface levels reflect a total cellular deficiency, we measured L-selectin in PMN lysates and plasma from cord and adult blood. L-selectin content was decreased in cord blood PMN lysates compared with those of adults by both Western blot analyses and ELISA (cord blood, 1195 +/- 160 pg/mL; adult, 1870 +/- 260 pg/mL; X +/- SEM; p < 0.05). Soluble L-selectin levels were also decreased in cord blood plasma (324 +/- 24 ng/mL versus 537 +/- 28 ng/mLiter in adult plasma, p < 0.01). To evaluate L-selectin function, we next compared the dose dependent effect of several chemoattractants on shedding of L-selectin from cord blood and adult PMN. Adult PMN showed greater overall shedding of L-selectin as compared with cord blood PMN after stimulation with fMet-Leu-Phe (p < 0.03) and granulocyte-macrophage colony-stimulating factor (p < 0.02). In contrast, shedding of L-selectin was similar between groups after IL-8 tested stimulation. We conclude that cord blood PMN have a decreased cellular content of L-selectin in addition to an impaired ability to shed surface L-selectin in response to specific inflammatory mediators.
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PMID:Diminished soluble and total cellular L-selectin in cord blood is associated with its impaired shedding from activated neutrophils. 884 34

To determine the effect of growth factor mobilization on the expression of adhesion molecules, we compared CD34+ progenitor cell (PC) populations from steady-state bone marrow (BM) with granulocyte-macrophage colony-stimulating factor (GM-CSF)-mobilized apheresis products (peripheral blood stem cell (PSC)) using flow cytometry. To increase the accuracy of this analysis, CD34+ cells were enriched (MiniMACS) before cytometric analysis. A significantly lower expression of very late antigen-4 (VLA-4), leukocyte function antigen-1 (LFA-1) and LFA-3 were observed on PSC compared to BM CD34+ cells. In addition, significantly lower mean fluorescence intensity (MFI) of VLA-4, VLA-5, intercellular adhesion molecule-1 (ICAM-1), and sialyl Lewisx were observed on PSC as compared to BM CD34+ cells. Significantly higher levels of L-selectin and CD44 expression were observed on PSC as compared to BM CD34+ cells based on frequency and MFI (P < or = 0.05). In addition, the duration of GM-CSF administration or number of prior aphereses had no effect on adhesion molecule expression. These data suggest that decreased expression of adhesion molecules including VLA-4, LFA-1, ICAM-1 and LFA-3 play a role in PC mobilization. Based on these studies, we suggest that PC mobilization occurs as a stochastic process and is associated with the selection of CD34+ cells with low adhesion molecule expression.
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PMID:GM-CSF-mobilized peripheral blood CD34+ cells differ from steady-state bone marrow CD34+ cells in adhesion molecule expression. 920 10

Monocyte activation in response to recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) was examined in vitro in septic shock patients. These monocytes exhibited a greater respiratory burst activity than monocytes from healthy subjects; the response to secondary stimulation with bacterial stimuli was attenuated. GM-CSF restored the ability of monocytes to respond appropriately to secondary stimulation. Expression of certain integrin adhesion molecules, L-selectin, and Fcgamma receptors was increased on monocytes of septic shock patients; expression of CD11c was reduced. GM-CSF up-regulated integrin expression and decreased L-selectin, FcgammaRII, and FcgammaRIII expression. Septic patients exhibited greater biologic activity of monocyte tissue factor than did healthy subjects. Priming monocytes with GM-CSF accelerated tissue factor activation following stimulation with lipopolysaccharide and bacterial culture supernatant. Certain parameters of monocyte function may be restored by exposure to GM-CSF. This benefit may be offset by an increase in monocyte procoagulant activity.
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PMID:Granulocyte-macrophage colony-stimulating factor induces activation and restores respiratory burst activity in monocytes from septic patients. 941 77

Budesonide and formoterol are extensively used in current asthma therapy. Budesonide is known as potent antiinflammatory agent and formoterol also appears to have some antiinflammatory properties. We investigated inhibitory effects of these drugs on eosinophil activation in vitro as induced by fibroblast-conditioned medium (FCM). We measured the modulation of expression of clonal designator (CD)11b and L-selectin with flow cytometry after 4 h or 16 h of culture of eosinophils when budesonide or formoterol was applied either directly to the eosinophils while they were stimulated with FCM (direct method) or when each drug was applied to lung fibroblasts from which conditioned medium was then administered to eosinophils (indirect method). In the direct method, budesonide (10(-)(8) M) inhibited the modulation of CD11b (44 [25th to 75th percentiles: 26 to 66]% of control) and L-selectin (30 [-13 to 48]% of control) only after 16 h, and not after 4 h. Formoterol did not directly inhibit the modulation of eosinophil CD11b and L-selectin expression. In the indirect method, both budesonide and formoterol inhibited lung fibroblast activation, resulting in diminished eosinophil activation after 4 h. Budesonide or formoterol at 10(-)(8) M inhibited upregulation of CD11b to 26 [15 to 40]% and 38 [23 to 46]%, respectively, and inhibited L-selectin shedding to 14 [-3 to 50]% and 27 [2 to 62]%, respectively, of control values. These results show that budesonide inhibits eosinophil activation primarily through effects on lung fibroblasts, presumably by inhibiting production of granulocyte-macrophage colony-stimulating factor. After longer incubation periods, budesonide also directly inhibits eosinophil activation. In contrast, formoterol can inhibit eosinophil activation only via inhibitory effects on lung fibroblasts. We did not observe an additional effect of formoterol, beyond the effects induced by budesonide under any circumstance studied. Lung fibroblasts, in addition to eosinophils, may serve as important target cells for antiinflammatory treatment in asthma.
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PMID:Effects of budesonide and formoterol on eosinophil activation induced by human lung fibroblasts. 1102 22

Peripheral blood stem cells (PBSC) have become the preferred source of stem cells for autologous transplantation because of the technical advantage and the shorter time to engraftment. Administration of hematopoietic growth factors such as granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) results in mobilization of PBSCs into the peripheral blood. G-CSF and GM-CSF differ somewhat in the number and composition of CD34(+) cells and effector cells mobilized to the peripheral blood; however, the molecular mechanism underlying the release and engraftment of CD34(+) cells by these growth factors is poorly understood. This review provides a recent update on the involvement of hematopoietic growth factors, chemokines, adhesion molecules, and chemokine receptors in the regulation of stem cell release and engraftment. The involvement of very late antigen-4 (VLA-4), VLA-5, leukocyte function associated-1 molecule (LFA-1), and L-selectin and their receptors CXCR4 and its ligand SDF-1 will be discussed, and cross talk between these factors will also be reviewed in the context of stem cell release and engraftment. Finally, PBSC mobilization by chemokines will be reviewed in relation to hematopoietic growth factors.
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PMID:Recent developments in the regulation of peripheral blood stem cell mobilization and engraftment by cytokines, chemokines, and adhesion molecules. 1135 70

The first immune cell to arrive at the site of infection is the neutrophil. Upon arrival, neutrophils quickly initiate microbicidal functions, including the production of antimicrobial products and proinflammatory cytokines that serve to contain infection. This allows the acquired immune system enough time to generate sterilizing immunity and memory. Neutrophils detect the presence of a pathogen through germ line-encoded receptors that recognize microbe-associated molecular patterns. In vertebrates, the best characterized of these receptors are Toll-like receptors (TLRs). We have determined the expression and function of TLRs in freshly isolated human neutrophils. Neutrophils expressed TLR1, 2, 4, 5, 6, 7, 8, 9, and 10-all the TLRs except TLR3. Granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment increased TLR2 and TLR9 expression levels. The agonists of all TLRs expressed in neutrophils triggered or primed cytokine release, superoxide generation, and L-selectin shedding, while inhibiting chemotaxis to interleukin-8 (IL-8) and increasing phagocytosis of opsonized latex beads. The response to the TLR9 agonist nonmethylated CpG-motif-containing DNA (CpG DNA) required GM-CSF pretreatment, which also enhanced the response to the other TLR agonists. Finally, using quantitative polymerase chain reaction (QPCR), we demonstrate a chemokine expression profile that suggests that TLR-stimulated neutrophils recruit innate, but not acquired, immune cells to sites of infection.
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PMID:Toll-like receptors stimulate human neutrophil function. 1282 92