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)

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

Dendritic cells (DC) are migratory cells which exhibit complex trafficking properties in vivo, involving interaction with vascular and lymphatic endothelium and extracellular matrix (ECM). The underlying mechanisms involved in these processes are still ill defined. In the present study we have investigated the ability of DC to interact in vitro with human vascular endothelial cells (EC) and ECM. DC were differentiated from monocytes by in vitro exposure to granulocyte-macrophage colony-stimulating factor and interleukin-13 for 7 days. In adhesion assays a considerable proportion of DC bound to resting EC monolayers: (17% +/- 4%, mean +/- SE of eight experiments). Adhesion to tumor necrosis factor (TNF)-activated EC was increased to 29% +/- 5% (n = 8). Binding to resting EC was strongly inhibited by anti-CD11a and CD11b, but not by CD11c monoclonal antibodies (MoAbs); on TNF-activated EC, anti-VLA-4 in concert with anti-CD18 inhibited adhesion by more than 70%. Binding to a natural ECM, derived from cultured EC, or to purified fibronectin was high: 52% +/- 6% (n = 8) involved VLA-4 and VLA-5 integrins. In a transmigration assay, 10% +/- 2% (n = 6) of input cells were able to cross the EC monolayer. Unlike adhesion, transendothelial migration was significantly reduced by anti-CD31 MoAb. The amount of DC transmigrated through a monolayer of EC was increased twofold to threefold by a defined set of C-C chemokines including RANTES, MIP1alpha, MIP5, and, to a lesser extent, by MIP1beta and MCP-3. Most importantly, in view of the trafficking pattern of these cells, a significant proportion of DC (13% +/- 4% of input cells seeded) was able to migrate across the endothelial basement membrane and, subsequently, across the endothelial barrier (reverse transmigration). The adhesion molecules and chemoattractants characterized herein are likely to underlie the complex trafficking of DC in vivo.
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PMID:Adhesion, transendothelial migration, and reverse transmigration of in vitro cultured dendritic cells. 963 18

We studied the phenotypic characteristics of spontaneously migrated skin dendritic cells (sDC) and monocyte-derived dendritic cells (moDC), generated under different culture conditions, and their interactions with fibronectin (FN) and endothelial cells. Monocyte-derived dendritic cells were obtained after culturing monocytes with granulocyte-macrophage colony-stimulating factor (GM-CSF) (800 U/ml) and interleukin-4 (IL-4) (500 U/ml) with either 10% fetal bovine serum (FBS) or 10% allogeneic human serum (HS). Regardless of the type of serum used, the majority of moDC expressed human leucocyte antigen-DR (HLA-DR) and CD86. On day 5 of incubation, 20-67% of moDC cultured in the presence of HS (HS-moDC) expressed CD1a, b and c versus 94-97% when cultured in the presence of FBS (FBS-moDC). DC showed a differential gradient of adhesion to FN: FBS-moDC>HS-moDC>sDC approximately monocytes. Both FBS-moDC and HS-moDC were strongly positive for CD49e (alpha5-integrin) and CD29 (beta1-integrin) but negative for CD49d (alpha4-integrin). A monoclonal antibody (mAb) against CD49e blocked the adhesion of both types of moDC to FN. Although both FBS-moDC and HS-moDC attached to endothelium (a 76% and 63% increase, respectively), only HS-moDC were able to migrate through non-activated endothelium. Overall, these results suggest that spontaneously migrated sDC are less adherent to FN than moDC, that HS and FBS induce differences in CD1 expression, that HS-moDC are less adhesive to FN and endothelial cells but more motile than FBS-moDC, and that alpha5beta1-integrin is the molecule involved in moDC adhesion to FN.
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PMID:Interactions of dendritic cells with fibronectin and endothelial cells. 982 88

Human monocyte-derived dendritic cells (MoDCs) obtained from peripheral blood monocytes (PBMC) cultured with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) can be activated in vitro by a variety of simple chemicals such as haptens and several metals. Recently, it has been demonstrated that transforming growth factor-beta1 (TGF-beta1) can induce further differentiation of MoDCs to the cells that share some characteristics with epidermal Langerhans cells, i.e. they contain Birbeck granules and express E-cadherin. In this study, using such TGF-beta1-treated dendritic cells (TGF-beta1+ DCs), we examined the in vitro effects of representative haptens, i.e. NiCl2 and dinitrochlorobenzene (DNCB), on their phenotypic and functional characteristics, comparing with those reported in vivo in epidermal Langerhans cells during the sensitization phase of a contact sensitivity reaction. Treatment of TGF-beta1+ DCs with NiCl2 increased their expression of the molecules related to antigen presentation such as CD86, major histocompatibility complex class I and class II, and CD83, although weakly, in addition to that of those essential for their migration to the regional lymph nodes, such as CD49e, CD44 and its variant 6, while it down-regulated the expression of the molecules required for homing to the skin and staying in the epidermis, such as cutaneous leucocyte antigen (CLA) and E-cadherin. It also increased the production of tumour necrosis factor-alpha, but not that of IL-1beta or IL-12. DNCB also increased their CD86 expression and down-regulated E-cadherin and CLA, but did not affect other phenotypic changes that were observed in TGF-beta1+ DCs treated with NiCl2. TGF-beta1+ DCs treated with either NiCl2 or DNCB increased their allogeneic T-cell stimulatory function. In addition, reverse transcribed polymerase chain reaction revealed augmented expression of chemokine receptor 7 mRNA by TGF-beta1+ DCs when treated with either NiCl2 or DNCB. Moreover, consistent with this data, TGF-beta1+ DCs treated with these chemicals chemotactically responded to macrophage inflammatory protein-3beta. These data suggest the possibility that TGF-beta1+ DCs present a good in vitro model to study the biology of epidermal Langerhans cells.
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PMID:In vitro treatment of human transforming growth factor-beta1-treated monocyte-derived dendritic cells with haptens can induce the phenotypic and functional changes similar to epidermal Langerhans cells in the initiation phase of allergic contact sensitivity reaction. 1101 55

We recently located a rare cytokeratin-positive (CK+) type of microvascular endothelial cell (MVEC) in the corpus luteum and aorta. Bovine corpus luteum MVEC are known to be involved in the cyclic accumulation of eosinophils and macrophages. Since leukocyte migration is specifically mediated by adhesion molecules and the release of cytokines, we compared the expression of these factors in basal and TNF-alpha-stimulated CK+ MVEC and in common cytokeratin-negative (CK-) MVEC in order to obtain an initial insight into the functional capacities of CK+ MVEC. CK- MVEC revealed significantly higher basal RANTES mRNA expression than CK+ MVEC, and TNF- alpha up-regulated RANTES mRNA in both types of MVEC. Only resting and stimulated CK- MVEC expressed granulocyte-macrophage colony-stimulating factor mRNA. Both MVEC types expressed monocyte colony-stimulating factor mRNA, but remained negative for eotaxin and interleukin (IL)-5 mRNA even after stimulation. Resting CK+ MVEC were positive for CD29, CD31, CD49a and CD49e, but expressed most of these antigens at a significantly lower density than did CK- MVEC. In contrast to CK- MVEC, CK+ MVEC failed to express CD49b or MHC class II. The activation of CK+ MVEC with TNF-alpha induced the expression of CD62P, but not of CD49b or MHC class II. In summary, phenotypically variable MVEC derived from the microvascular bed of one organ differ in their TNF-alpha-regulated expression of cytokine mRNA and adhesion molecules. Morphological heterogeneity is related to a particular specialisation of functional MVEC.
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PMID:Microvascular endothelial cells differ in their basal and tumour necrosis factor-alpha-regulated expression of adhesion molecules and cytokines. 1102 4

We have previously reported that the priming of thioglycollate-elicited peritoneal macrophages (PMphi), as a representative population of mononuclear phagocytes (MNP), by macrophage-colony-stimulating factor (M-CSF or CSF-1) rendered these cells more susceptible to secondary stimulation by extracellular matrix (ECM) proteins, in particular fibronectin (FN), and that at least two beta1 integrins, VLA 4 (alpha4beta1 or CD49d) and VLA 5 (alpha5beta1 or CD49e), regulate IL-6 gene expression when PMphi come into contact with FN. In this report, we focused our attention on resident PMphi, as a more mature/differentiated MNP subpopulation. By using granulocyte-macrophage colony-stimulating factor (GM-CSF)- and IL-6-knockout (null) mice, we demonstrated that the cooperative effect between CSF-1 and FN in IL-6 release was a result of a sequential stimulation of the GM-CSF, but not the TNF-alpha, gene via interaction with VLA 5. We also showed that regardless of the presence or absence of CSF-1 or FN, IL-6 inhibits GM-CSF and TNF-alpha gene expression in an autocrine manner. The observed effects were specific because CSF-1 enhanced VLA 5 expression and blocking FN-treated resident PMphi in vitro with VLA 5 monoclonal antibodies inhibited the IL-6 response. We found that treatment of resident PMphi with the protein kinase C inhibitor, staurosporine, and the activator, phorbol myristate acetate (PMA), resulted in marked modulation of either FN- or FN/CSF-1-induced cytokine release. An increased level of VLA 5 expression was observed in PMA-treated resident PMphi. We concluded that in inflammatory processes, CSF-1 drives a number of pathways involved in the regulation of the expression of several genes and renders MNP highly susceptible to stimulation by ECM proteins that transform the MNP into secretory inflammatory cells.
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PMID:CSF-1 (M-CSF) enhances the inflammatory response of fibronectin-primed macrophages: pathways involved in activation of the cytokine network. 1106 91

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