Published online before print February 2, 2006, doi: 10.1161/01.RES.0000207393.67851.d4
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Submitted on October 4, 2005
Revised on December 21, 2005
Accepted on January 20, 2006
Platelet-Derived Growth Factor BB-Mediated Normalization of Dermal Interstitial Fluid Pressure After Mast Cell Degranulation Depends on 
3 but Not 1 Integrins
Åsa Lidén ;
From the Department of Medical Biochemistry and Microbiology (A.L., K.R.), University of Uppsala, Sweden; and the Department of Biomedicine (A.B., T.N., R.K.R.), Division of Physiology, University of Bergen, Norway.
* To whom correspondence should be addressed. E-mail: Kristofer.Rubin{at}imbim.uu.se.
Interstitial fluid pressure (PIF) is 1 of the determinants of transcapillary fluid flux and thereby interstitial fluid volume. Cell-mediated control of PIF regulates fluid content in the loose interstitial connective tissues that surround the capillary bed. To maintain a normal PIF in dermis, 
1 integrins mediate the tensile strength applied by connective tissue cells on the extracellular matrix. Platelet-derived growth factor (PDGF)-BB normalizes anaphylaxis-induced reduction of PIF. Anti-3 integrin IgG and a cyclic RGD peptide that inhibits the 
V3 integrin blocked the ability of PDGF-BB to normalize the lowered PIF resulting from mast cell degranulation. PDGF-BB was unable to normalize PIF lowered as a result of mast cell degranulation in 3-negative mice. Monoclonal anti-3 integrin IgG had no effect on PIF in normal mouse dermis. In contrast, administration of anti-1 integrin IgM lowered PIF in normal dermis but had no effect on PDGF-BB-induced normalization of PIF after anaphylaxis. Furthermore, collagen gel contraction mediated by wild-type mouse embryonal fibroblasts were only marginally affected by function-blocking anti-1 integrin antibodies, especially in the presence of PDGF-BB. In contrast, contraction mediated by V-negative mouse embryonic fibroblasts was completely blocked by anti-1 integrin antibodies, even after stimulation with PDGF-BB. These results show a previously unrecognized in vivo function for the V3 integrin, as a participant in the control of PIF during inflammatory reactions. Furthermore, our data demonstrate that PDGF-BB induces connective tissue cells to generate tensile forces via V3 during such reactions.
Key words: anaphylaxis •
V integrins •
collagen gel contraction •
edema •
fluid homeostasis
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