The α11β1 Integrin Has a Mechanistic Role in Control of Interstitial Fluid Pressure and Edema Formation in Inflammation

Objective-Collagen-binding integrins may be involved in controlling interstitial fluid pressure (Pif), transcapillary fluid flux, and tissue fluid volume. Our aim was to explore whether the newly discovered collagen binding alpha 11 beta 1 integrin has a mechanistic role in inflammatory edema formation. Methods and Results-In collagen matrices seeded with a mixture of mast cells and fibroblasts, fibroblasts lacking the alpha 11 integrin subunit (alpha 11(-/-)) contracted collagen gels less efficiently than control fibroblasts, suggesting that the alpha 11 beta 1 integrin is able to mediate tensile force in connective tissues. In alpha 11(-/-) mice, control Pif in skin did not differ from the pressure found in wild-type mice. Whereas a reduction in Pif was found in control mice after inducing inflammation, thereby contributing to fluid extravasation and edema formation, such a reduction was not seen in alpha 11(-/-) mice. That this effect is mediated through the extracellular compartment is suggested by a similar plasma protein extravasation ratio in alpha 11(-/-) and wild-type mice. Conclusions-Our data suggest that alpha 11 beta 1 integrins on dermal fibroblasts mediate collagen lattice remodeling and have a mechanistic role in controlling Pif in inflammation and thereby fluid extravasation and edema formation in vivo. (Arterioscler Thromb Vasc Biol. 2009; 29: 1864-1870.)