Rodt S A, Reed R K, Ljungström M, Gustafsson T O, Rubin K
Department of Physiology, University of Bergen, Norway.
Circ Res. 1994 Nov;75(5):942-8. doi: 10.1161/01.res.75.5.942.
Edema formation in acute inflammation can be induced through lowering of interstitial fluid pressure (Pif) 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 Pif. The anti-inflammatory drug alpha-trinositol (1,2,6-D-myo-inositol trisphosphate) stabilizes Pif in acute inflammation. Pretreatment with 5 mg IV alpha-trinositol in pentobarbital-anesthetized rats inhibited the lowering in Pif 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 Pif 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 Pif in vivo.
急性炎症中水肿的形成可通过降低组织间隙液压力（Pif）诱导，且似乎涉及真皮细胞与细胞外基质纤维之间由β1整合素介导的动态相互作用。本实验研究β1整合素在Pif调控中的作用。抗炎药物α-三磷酸肌醇（1,2,6-D-肌醇三磷酸）可在急性炎症中稳定Pif。在戊巴比妥麻醉的大鼠中静脉注射5mgα-三磷酸肌醇进行预处理，可抑制皮下注射抗β1整合素IgG所诱导的Pif降低和水肿形成。α-三磷酸肌醇在体内对β1整合素功能的这种稳定作用，与它在体外对成纤维细胞填充的三维胶原晶格收缩的影响相平行。在胶原凝胶收缩试验中，α-三磷酸肌醇与血小板衍生生长因子-BB对最终凝胶大小的已知刺激作用具有相加性。此外，α-三磷酸肌醇抵消了抗β1整合素Fab片段对胶原凝胶收缩的抑制作用。最后，皮下注射二丁酰环磷腺苷（db-cAMP）诱导的Pif负性增加程度与抗β1整合素抗体相同，且在体外db-cAMP降低了成纤维细胞收缩胶原凝胶的能力。α-三磷酸肌醇可对抗后一种作用。数据表明，α-三磷酸肌醇可调节β1整合素功能，可能是通过细胞内途径进而影响β1整合素的功能和/或细胞表面表达，并提示α-三磷酸肌醇可作为研究整合素功能的工具。此外，数据表明胶原收缩试验可能为体内Pif的调控提供重要信息。
