Regulation of alpha 2 beta 1-mediated fibroblast migration on type I collagen by shifts in the concentrations of extracellular Mg2+ and Ca2+.
Extracellular Ca2+ can reverse the Mg(2+)-dependent, alpha 2 beta 1-mediated adhesion of WI38 human fibroblasts to type I collagen substrates. Affinity chromatography data also demonstrate that Ca2+ can specifically elute the fibroblast alpha 2 beta 1 integrin bound to type I collagen-Sepharose in Mg2+. In modified Boyden chamber migration assays, Mg2+ alone supports the alpha 2 beta 1-mediated migration of fibroblasts on type I collagen substrates, while Ca2+ does not. However, a twofold enhancement in migration was observed when combinations of the two cations were used, with optimal migration observed when the Mg2+/Ca2+ ratio was higher than one. Inhibitory mAbs directed against various integrin subunits demonstrate that these observed cation effects appear to be mediated primarily by alpha 2 beta 1. These data, together with reports that under certain physiological conditions significant fluctuations in the concentrations of extracellular Ca2+ and Mg2+ can take place in vivo, suggest that the ratio between these two cations is involved in the up- and downregulation of integrin function, and thus, may influence cell migratory behavior.
Grzesiak
J J
JJ
La Jolla Cancer Research Foundation, California 92037.
Davis
G E
GE
Kirchhofer
D
D
Pierschbacher
M D
MD
D000595:Amino Acid Sequence; D002118:Calcium / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects*; D002846:Chromatography, Affinity; D003094:Collagen / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005347:Fibroblasts; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000276:immunology / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology*; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D019096:Vitronectin
D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D016023:Integrins; D019096:Vitronectin; D003094:Collagen; D008274:Magnesium; D002118:Calcium