The 11 1 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 11 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 11 integrin subunit ( 11 / ) contracted collagen gels less efficiently than control fibroblasts, suggesting that the 11 1 integrin is able to mediate tensile force in connective tissues. In 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 11 / mice. That this effect is mediated through the extracellular compartment is suggested by a similar plasma protein extravasation ratio in 11 / and wild-type mice. Conclusions—Our data suggest that 11 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.)