Integrin alpha(V)beta(3) can substitute for collagen-binding beta(1)-integrins in vivo to maintain a homeostatic interstitial fluid pressurel

• Accumulated data indicate that cell-mediated contraction of reconstituted collagenous gels in vitro can serve as a model for cell-mediated control of interstitial fluid pressure (P-IF) in vivo. A central role for collagen-binding beta(1)-integrins in both processes has been established. Furthermore, integrin alpha(V beta 3) takes over the role of collagen-binding beta(1)-integrins in mediating contraction after perturbations of collagen-binding beta(1)-integrins in vitro. Integrin alpha(V beta 3) is also instrumental for normalization of dermal P-IF that has been lowered due to mast cell degranulation with compound 48/80 (C48/80) in vivo. Here we demonstrate a role of integrin alpha(V)beta(3) in maintaining a long term homeostatic dermal P-IF in mice lacking the collagen-binding integrin alpha(111) (alpha 11(-/-) mice). Measurements of P-IF were performed after circulatory arrest. Furthermore, cell-mediated integrin alpha(V)beta(3)-directed contraction of collagenous gels in vitro depends on free access to a collagen site known to bind several extracellular matrix (ECM) proteins that form substrates for (V3)-directed cell attachment, such as fibronectin and fibrin. A streptococcal collagen-binding protein, CNE, specifically binds to and blocks this site on the collagen triple helix. Here we show that whereas CNE perturbed alpha(V beta 3)-directed and platelet-derived growth factor BB-induced normalization of dermal P-IF after C48/80, it did not affect alpha(V beta 3)-dependent maintenance of a homeostatic dermal P-IF. These data imply that dynamic modification of the ECM structure is needed during acute patho-physiological modulations of P-IF but not for long-term maintenance of a homeostatic P-IF. Our data thus show that collagen-binding beta(1)-integrins, integrin alpha(V)beta(3) and ECM structure are potential targets for novel therapy aimed at modulating oedema formation and hypovolemic shock during anaphylaxis.

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MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

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