Fries Erik, Kaczmarczyk Aneta
Department of Medical Biochemistry and Microbiology, Uppsala University, BMC, Uppsala, Sweden.
Acta Biochim Pol. 2003;50(3):735-42.
Inter-alpha-inhibitor is an abundant plasma protein whose physiological function is only now beginning to be revealed. It consists of three polypeptides: two heavy chains and one light chain called bikunin. Bikunin, which has antiproteolytic activity, carries a chondroitin sulphate chain to which the heavy chains are covalently linked. The heavy chains can be transferred from inter-alpha-inhibitor to hyaluronan molecules and become covalently linked. This reaction seems to be mediated by TSG-6, a protein secreted by various cells upon stimulation by inflammatory cytokines. Inter-alpha-inhibitor has been shown to be required for the stabilization of the cumulus cell-oocyte complex during the expansion that occurs prior to ovulation. Hyaluronan-linked heavy chains in the extracellular matrix of this cellular complex have recently been shown to be tightly bound to TSG-6. Since TSG-6 binds to hyaluronan, its complex with heavy chains could stabilize the extracellular matrix by cross-linking hyaluronan molecules. Heavy chains linked to hyaluronan molecules have also been found in inflamed tissues. The physiological role of these complexes is not known but there are indications that they might protect hyaluronan against fragmentation by reactive oxygen species. TSG-6 also binds to bikunin thereby enhancing its antiplasmin activity. Taken together, these results suggest that inter-alpha-inhibitor is an anti-inflammatory agent which is activated by TSG-6.
α-间抑制因子是一种丰富的血浆蛋白，其生理功能直到现在才开始被揭示。它由三种多肽组成：两条重链和一条称为比基尼的轻链。具有抗蛋白水解活性的比基尼携带一条硫酸软骨素链，重链与之共价连接。重链可以从α-间抑制因子转移到透明质酸分子上并共价连接。这个反应似乎是由TSG-6介导的，TSG-6是一种在炎症细胞因子刺激下由各种细胞分泌的蛋白质。已证明α-间抑制因子在排卵前发生的卵丘细胞-卵母细胞复合体扩张过程中对其稳定是必需的。最近发现，这个细胞复合体的细胞外基质中与透明质酸相连的重链与TSG-6紧密结合。由于TSG-6与透明质酸结合，它与重链的复合物可以通过交联透明质酸分子来稳定细胞外基质。在炎症组织中也发现了与透明质酸分子相连的重链。这些复合物的生理作用尚不清楚，但有迹象表明它们可能保护透明质酸不被活性氧碎片化。TSG-6还与比基尼结合，从而增强其抗纤溶酶活性。综上所述，这些结果表明α-间抑制因子是一种由TSG-6激活的抗炎剂。
