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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:1864.)
© 2009 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

The 11β1 Integrin Has a Mechanistic Role in Control of Interstitial Fluid Pressure and Edema Formation in Inflammation

Ø.S. Svendsen; M.M. Barczyk; S.N. Popova; Å Lidén; D. Gullberg; H. Wiig

From the Department of Anesthesia and Intensive Care (Ø.S.S.), Haukeland University Hospital, and the Department of Biomedicine (Ø.S.S., M.M.B., S.N.P., Å.L., D.G., H.W.), University of Bergen, Norway.

Correspondence to Øyvind Sverre Svendsen, Department of Biomedicine, University of Bergen, Jonas Lies vei 91, N-5009 Bergen, Norway. E-mail Oyvind.Svendsen{at}biomed.uib.no

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 11β1 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 11β1 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 11β1 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.

11β1 integrins on fibroblasts are capable of increasing the contraction of collagen gels in vitro. 11^–/– mice, in contrast to wild-type mice, did not show a reduction in skin interstitial fluid pressure during acute inflammation, suggesting that the 11β1 integrin has a mechanistic role in edema formation during inflammation.

Key Words: collagen • endothelium • extracellular matrix • genetically altered mice • microcirculation