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急性期反应物C反应蛋白与纤连蛋白的结合

Binding of fibronectin by the acute phase reactant C-reactive protein.

作者信息

Salonen E M, Vartio T, Hedman K, Vaheri A

出版信息

J Biol Chem. 1984 Feb 10;259(3):1496-501.

PMID:6693419
Abstract

Following tissue injury, the concentration of C-reactive protein (CRP) is known to increase in plasma rapidly, while that of fibronectin often decreases. We now report that CRP immobilized onto polystyrene surfaces binds soluble plasma fibronectin (Kd = 1.5 X 10(-8) M). The binding of fibronectin by CRP was relatively sensitive to ionic conditions, being maximal at physiological NaCl concentrations. A decrease of pH from neutral to 5-6 greatly enhanced the binding of fibronectin by CRP. Ca2+ ions at greater than 1 mM inhibited binding. No binding was observed between fibronectin and CRP in soluble phase. CRP was found also to bind fibrinogen, which competed with fibronectin for CRP-binding sites. This was shown to explain why fibronectin was effectively bound from serum but not from plasma by immobilized CRP. The amount of CRP immobilized was critical in binding fibronectin; a too dense molecular layer of CRP inhibited the binding, as did the postsaturation of free surfaces with albumin, which itself was not bound by CRP. Soluble fibronectin agglutinated CRP-coated latex particles. Most or all of the CRP-binding activity in the fibronectin molecule was localized to the 120-140-kilodalton fragment, which also contains cell-binding and heparin-binding domains of fibronectin. The results provide a link between acute phase response and tissue repair.

摘要

组织损伤后,已知血浆中C反应蛋白(CRP)的浓度会迅速升高,而纤连蛋白的浓度通常会降低。我们现在报告,固定在聚苯乙烯表面的CRP能结合可溶性血浆纤连蛋白(解离常数Kd = 1.5×10⁻⁸ M)。CRP对纤连蛋白的结合相对受离子条件影响,在生理NaCl浓度下结合能力最强。pH从中性降至5 - 6会大大增强CRP对纤连蛋白的结合。高于1 mM的Ca²⁺离子会抑制结合。在可溶性相中未观察到纤连蛋白与CRP之间的结合。还发现CRP能结合纤维蛋白原,纤维蛋白原与纤连蛋白竞争CRP的结合位点。这就解释了为什么固定化的CRP能有效从血清中结合纤连蛋白,却不能从血浆中结合。固定化CRP的量对于结合纤连蛋白至关重要;CRP分子层过密会抑制结合,用白蛋白对自由表面进行后饱和处理也会抑制结合,而白蛋白本身不会被CRP结合。可溶性纤连蛋白能凝集包被CRP的乳胶颗粒。纤连蛋白分子中大部分或全部的CRP结合活性定位于120 - 140千道尔顿的片段,该片段还包含纤连蛋白的细胞结合域和肝素结合域。这些结果为急性期反应和组织修复之间建立了联系。

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