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 Mg2+-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.