Swarnakar S, Asokan R, Quigley J P, Armstrong P B
Department of Pharmacological Sciences, Health Sciences Center, BHS, Level 7, Room 140, State University of New York, Stony Brook, NY 11794, USA.
Biochem J. 2000 May 1;347 Pt 3(Pt 3):679-85.
The mediator of haemolysis in the plasma of the horseshoe crab, Limulus polyphemus, is limulin, a sialic acid-binding lectin. The haemolytic activity of limulin is inhibited by thiol ester-reacted forms of Limulus alpha(2)-macroglobulin, the third-most abundant protein of the plasma. Limulus alpha(2)-macroglobulin that has experienced cleavage of its internal thiol ester bond, consequent to reaction with proteases, or with the small primary amine, methylamine, reduces the haemolytic activity of limulin when present at molar excesses that approximate the relative concentrations of these two proteins in the plasma. Native, unreacted Limulus alpha(2)-macroglobulin has no effect on the haemolytic activity of limulin. Limulin binds thiol ester-reacted forms of Limulus alpha(2)-macroglobulin both in a solid-phase assay and in solution with an avidity 10-25 times higher than native, unreacted Limulus alpha(2)-macroglobulin. Protease-reacted alpha(2)-macroglobulin functions as a marker for the presence of foreign proteases in the blood of Limulus, and thus of pathogenic organisms that release proteases as facilitators of invasion and pathogenicity. Modulation of the haemolytic system represents a novel function for alpha(2)-macroglobulin.
鲎(美洲鲎)血浆中的溶血介质是鲎素,一种唾液酸结合凝集素。鲎素的溶血活性受到鲎α2-巨球蛋白硫酯反应形式的抑制,鲎α2-巨球蛋白是血浆中含量第三丰富的蛋白质。与蛋白酶或小伯胺甲胺反应后,其内部硫酯键发生断裂的鲎α2-巨球蛋白,当以接近血浆中这两种蛋白质相对浓度的摩尔过量存在时,会降低鲎素的溶血活性。天然的、未反应的鲎α2-巨球蛋白对鲎素的溶血活性没有影响。在固相测定和溶液中,鲎素与鲎α2-巨球蛋白的硫酯反应形式结合,亲和力比天然的、未反应的鲎α2-巨球蛋白高10至25倍。蛋白酶反应后的α2-巨球蛋白可作为鲎血液中存在外源蛋白酶的标志物,从而作为释放蛋白酶以促进入侵和致病性的致病生物的标志物。溶血系统的调节代表了α2-巨球蛋白的一种新功能。