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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)

Connective tissue cells (myofibroblasts) from liver inflammatory granulomatous reactions to schistosome eggs are able to sustain a long-term proliferation of myeloid cells, both in vivo and in vitro. We have addressed the question of the molecular mechanisms involved in control of this extramedullar stroma-dependent production of inflammatory cells. Heparan sulfate proteoglycans (HSPGs) were purified from granuloma-derived connective tissue cells and bound to plastic or collagen substrate. Their ability to bind recombinant murine granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3), to stimulate proliferation of the FDC-P1 myeloid cell lineage, and to modify growth factor activity was monitored. The specificity of this stroma cell-derived glycosaminoglycan interaction with the myeloid growth factors was analyzed by comparing other glycosaminoglycans and sulfated polysaccharides. HSPGs could act as an artificial myelopoietic stroma; they were both required and sufficient for binding and presenting GM-CSF and IL-3 in biologically active form. Moreover, they were able to mediate an increase in the specific growth-promoting activity of GM-CSF and IL-3. This was specific for stroma-derived heparan sulfate and heparin, since heparan sulfate derived from other cells, other glycosaminoglycans and related molecules had no effect. These results indicate that HSPGs can stimulate and control the in situ proliferation of myeloid cells, modifying in both quantitative and qualitative terms the composition of inflammatory cell infiltrates in hepatic granulomas.
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PMID:GM-CSF and IL-3 activities in schistosomal liver granulomas are controlled by stroma-associated heparan sulfate proteoglycans. 860 24

We recently demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) is an autocrine growth factor for human osteoblastic (hOB) cells. Since GM-CSF is a member of the heparin-binding factor family, we examined the interactions between GM-CSF and glycosaminoglycans (GAGs) present in the osteoblast microenvironment. Using a bioassay in which the mitogenic activity of recombinant human (rh) GM-CSF was measured after incubation in the presence of an hOB cell layer or extracellular matrix (ECM) produced by these cells, we showed that rhGM-CSF binds to GAG components present in the ECM and that the bound rhGM-CSF retains its ability to stimulate hOB cell proliferation. Heparan sulfate compounds on the hOB cell surface were also found to sequester GM-CSF. Moreover, treatment with sodium chlorate, an inhibitor of GAG sulfation, suppressed the mitogenic activity of rhGM-CSF on hOB cells. This inhibitory effect was rescued by a low dose of heparin. Heparin was also found to promote the effect of rhGM-CSF on hOB cell proliferation, allowing nonmitogenic high doses of rhGM-CSF to stimulate hOB cell growth. Western blot analysis showed that undersulfation of cellular GAGs by chlorate inhibited the increased tyrosine phosphorylation of proteins involved in GM-CSF signaling in cloned immortalized hOB cells. The data demonstrate that GM-CSF binds to proteoglycans on the hOB cell surface and in ECM produced by these cells and that the bound GM-CSF is biologically active. Furthermore, this study shows that cellular proteoglycans play an essential role in GM-CSF signaling and biological activity in hOBs.
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PMID:Glycosaminoglycans bind granulocyte-macrophage colony-stimulating factor and modulate its mitogenic activity and signaling in human osteoblastic cells. 973 58