THE ANTIINFLAMMATORY AGENT ALPHA-TRINOSITOL EXERTS ITS EDEMA-PREVENTING EFFECT THROUGH MODULATION OF BETA(1) INTEGRIN FUNCTION

被引:49
作者
RODT, SA
REED, RK
LJUNGSTROM, M
GUSTAFSSON, TO
RUBIN, K
机构
[1] UNIV BERGEN, DEPT PHYSIOL, N-5009 BERGEN, NORWAY
[2] UPPSALA UNIV, DEPT MED & PHYSIOL CHEM, UPPSALA, SWEDEN
[3] PERSTORP PHARMA, LUND, SWEDEN
关键词
COLLAGEN GEL; CONNECTIVE TISSUE; INTEGRIN; INTERSTITIUM; PLATELET-DERIVED GROWTH FACTOR;
D O I
10.1161/01.RES.75.5.942
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Edema formation in acute inflammation can be induced through lowering of interstitial fluid pressure (P-if) and seems to involve dynamic beta(1) integrin-mediated interactions between dermal cells and extracellular matrix fibers. The present experiments investigate the role of beta(1) integrins in the control of P-if. The anti-inflammatory drug alpha-trinositol (1,2,6-D-myo-inositol trisphosphate) stabilizes P-if in acute inflammation. Pretreatment with 5 mg IV alpha-trinositol in pentobarbital-anesthetized rats inhibited the lowering in P-if and the edema formation induced by subdermal injection of anti-beta(1) integrin IgG. This stabilization of the beta(1) integrin function in vivo was paralleled by effects of alpha-trinositol on contraction of fibroblast-populated three-dimensional collagen lattices in vitro. alpha-Trinositol was additive to the known stimulatory effect of platelet-derived growth factor-BB on the final gel size in the collagen gel contraction assay. Furthermore, alpha-trinositol counteracted the inhibitory effect of anti-beta(1) integrin Fab fragments on collagen gel contraction. Finally, subdermal injection of dibutyryl-cAMP (db-cAMP) induced increased negativity of P-if to the same extent as did anti-beta(1) integrin antibodies, and in vitro db-cAMP reduced the ability of fibroblasts to contract collagen gels. The latter effect was opposed by alpha-trinositol. The data demonstrate that alpha-trinositol modulates beta(1) integrin function and may do so via intracellular pathways in turn affecting the function and/or cell surface expression of beta(1) integrins and suggest that alpha-trinositol can serve as a tool to study integrin function. Furthermore, the data indicate that the collagen contraction assays may provide important information of the control of P-if in vivo.
引用
收藏
页码:942 / 948
页数:7
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