The alpha11beta1 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 alpha11beta1 integrin has a mechanistic role in inflammatory edema formation.


RESULTS
In collagen matrices seeded with a mixture of mast cells and fibroblasts, fibroblasts lacking the alpha11 integrin subunit (alpha11(-/-)) contracted collagen gels less efficiently than control fibroblasts, suggesting that the alpha11beta1 integrin is able to mediate tensile force in connective tissues. In alpha11(-/-) 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 alpha11(-/-) mice. That this effect is mediated through the extracellular compartment is suggested by a similar plasma protein extravasation ratio in alpha11(-/-) and wild-type mice.


CONCLUSIONS
Our data suggest that alpha11beta1 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.
Svendsen
Ø S
ØS
Department of Anesthesia and Intensive Care, Haukeland University Hospital, Department of Biomedicine, University of Bergen, Bergen, Norway. Oyvind.Svendsen@biomed.uib.no
Barczyk
M M
MM
Popova
S N
SN
Lidén
A
A
Gullberg
D
D
Wiig
H
H
D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004487:Edema / Q000378:metabolism*; D045604:Extracellular Fluid / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism*; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011312:Pressure; D011897:Random Allocation; D038981:Receptors, Collagen / Q000378:metabolism*; D012016:Reference Values; D012680:Sensitivity and Specificity; D014162:Transfection
D016023:Integrins; D038981:Receptors, Collagen; C467800:integrin alpha11beta1; D003094:Collagen