Granulocyte-macrophage and macrophage colony-stimulating factors differentially regulate alpha v integrin expression on cultured human macrophages.
The colony-stimulating factors (CSFs) greatly influence mature macrophage function in vitro: macrophage (M)-CSF induces maturation of monocytes and enhances differentiated cell function; granulocyte-macrophage (GM)-CSF stimulates a variety of antimicrobial functions. In vivo M-CSF is thought to promote differentiation, and GM-CSF is thought to potentiate the inflammatory response. One mechanism by which these differential effects may be achieved is through the receptor-mediated interaction of macrophages with their extracellular matrix. Here we show that M-CSF induces specifically the expression of the alpha v beta 5 integrin receptor, whereas GM-CSF rapidly induces mRNA and surface expression of the alpha v beta 3 integrin. The M-CSF-treated cells acquire a flattened epitheloid phenotype, and on vitronectin the alpha v beta 5 is located in adhesion plaques. These cells do not bind collagen or laminin. In contrast, cells treated with GM-CSF adopt an elongated phenotype on a number of substrates, including collagen and laminin, and express alpha v beta 3 at the leading edge of cells on vitronectin. These results suggest that a primary means by which the CSFs exert their individual effects on mature cells may be through regulating integrin expression.
De Nichilo
M O
MO
Cancer Research Unit, Faculty of Medicine, University of Newcastle, N.S.W., Australia.
Burns
G F
GF
D000911:Antibodies, Monoclonal; D015152:Blotting, Northern; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D016326:Extracellular Matrix Proteins; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D016023:Integrins / Q000096:biosynthesis* / Q000235:genetics; D007700:Kinetics; D046911:Macromolecular Substances; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D019096:Vitronectin
D000911:Antibodies, Monoclonal; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D016023:Integrins; D046911:Macromolecular Substances; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019096:Vitronectin; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor