Mg2+ and Ca2+ differentially regulate beta 1 integrin-mediated adhesion of dermal fibroblasts and keratinocytes to various extracellular matrix proteins.
The specific requirements for divalent cations in the integrin-dependent adhesion and deadhesion of human dermal fibroblasts and human epidermal keratinocytes to various extracellular matrix proteins have been studied in vitro. The adhesion of both cell types to collagen type I and to laminin was enhanced by Mg2+ in a concentration-dependent manner, while Ca2+ dose-dependently antagonized this effect, thus promoting deadhesion. The cation-dependent conversion between adhesion and deadhesion occurred already at 2 to 10 min after addition of the alternate cation and was almost completed at 20 min. Interestingly, Ca2+ could not reverse the Mg(2+)-enhanced adhesion of both cell types to fibronectin. Inhibition studies with function-blocking antibodies directed against distinct beta 1 integrins showed that the Mg(2+)-enhanced fibroblast adhesion to collagen type I was mediated by the alpha 1 beta 1 and the alpha 2 beta 1 integrins, whereas keratinocyte adhesion to collagen type I was mediated by the alpha 2 beta 1 integrin. Both cell types utilized the alpha 2 beta 1 and the alpha 6 beta 1 integrins for Mg(2+)-dependent adhesion to laminin and the alpha 5 beta 1 integrin for the adhesion to fibronectin. Integrin expression at the cell surface was not altered, indicating that divalent cation-dependent conformational changes of beta 1 integrins most likely regulate their functional activity.
Lange
T S
TS
Department of Dermatology, University of Düsseldorf, Germany.
Bielinsky
A K
AK
Kirchberg
K
K
Bank
I
I
Herrmann
K
K
Krieg
T
T
Scharffetter-Kochanek
K
K
D002118:Calcium / Q000494:pharmacology; D002413:Cations, Divalent / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004347:Drug Interactions; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology*; D005353:Fibronectins / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D019012:Integrin beta1; D016023:Integrins / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000502:physiology*; D007797:Laminin / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D012867:Skin / Q000166:cytology; D012879:Skin Physiological Phenomena
D002413:Cations, Divalent; D005353:Fibronectins; D019012:Integrin beta1; D016023:Integrins; D007797:Laminin; D003094:Collagen; D008274:Magnesium; D002118:Calcium