Regulation of fibronectin receptor (alpha 5 beta 1) mRNA expression in human monocytes and monocyte-derived macrophages by activation/differentiation signals.
Members of the beta 1 subfamily of integrins, a group of heterodimeric transmembrane adhesion receptors, mediate the attachment of monocytes and macrophages to cell matrix proteins such as fibronectin, collagen, and laminin. Such interactions are likely of considerable importance during inflammatory responses, when monocytes are recruited to, and retained in, extravascular sites. Because of the complexity of the interactions that befall monocytes during an inflammatory response, it seems likely that expression of adhesion receptors on monocytes would be precisely regulated. In the present study, we have examined the mRNA expression of alpha 5 and beta 1 subunits of the fibronectin receptor in purified human peripheral blood monocytes and monocyte-derived macrophages cultured in the absence or presence of various agents known to induce activation and/or differentiation. Incubation under nonadherent conditions for 6 h with interferon (IFN)-gamma or bacterial lipopolysaccharide (LPS) resulted in a decreased expression of both alpha 5 and beta 1 mRNAs in freshly isolated monocytes. In contrast, incubation with IFN-alpha did not result in a decreased expression of alpha 5 mRNA, although a moderate decrease in beta 1 mRNA was observed. Culture with granulocyte-macrophage colony-stimulating factor, macrophage colony-stimulating factor, phorbol myristic acetate, or plasma fibronectin (under nonadherent and adherent conditions) did not result in a change in levels of alpha 5 or beta 1 transcripts. In contrast to the results obtained with freshly isolated monocytes, incubation for 6 h with IFN-gamma or LPS did not alter the expression of alpha 5 or beta 1 mRNA in macrophages derived by culture of monocytes for 6 days in Teflon beakers. Our results indicate that IFN-gamma and LPS, both of which may be present in inflammatory sites, downregulate the mRNA expression of fibronectin receptor subunits in monocytes. Moreover, alpha 5 and beta 1 gene regulation by these agents is apparently dependent on the differentiation stage of the cells. This may provide a mechanism by which extravasating monocytes detach from extracellular matrix proteins, present in subendothelial basement membranes and deposited in sites of inflammation, in order to pursue other activities.
Kohn
F R
FR
Terry Fox Laboratory for Hematology/Oncology, British Columbia Cancer Agency, Vancouver, Canada.
Klingemann
H G
HG
D002454:Cell Differentiation; D002478:Cells, Cultured; D005353:Fibronectins / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics*; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic / Q000235:genetics*; D011994:Recombinant Proteins
D005353:Fibronectins; D007370:Interferon Type I; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D017469:Receptors, Fibronectin; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; D007371:Interferon-gamma