Cole M F, Hale C A
Department of Microbiology, Georgetown University, School of Medicine, Washington, D.C. 20007.
Microb Pathog. 1991 Jul;11(1):39-46. doi: 10.1016/0882-4010(91)90092-o.
Immunoglobulin (Ig)A proteases synthesized by human mucosal pathogens have a unique specificity for human IgA and will not cleave IgA from other species. In contrast, animal pathogens have not reliably been shown to cleave IgA of the animals they infect. This lack of an animal model has prevented an understanding of the importance of IgA1 proteases as virulence factors. One strategy to develop an animal model would be to identify a species capable of infection by a human IgA-producing pathogen whose IgA was susceptible to cleavage by IgA1 protease of that bacterium. The chimpanzee can be infected with Haemophilus influenzae and is closely related immunologically to man. For these reasons it was sought to determine whether chimpanzee secretory IgA (SIgA) is susceptible to cleavage by IgA1 protease of H. influenzae. This report shows that chimpanzee SIgA can indeed be cleaved at the hinge region by H. influenzae IgA1 protease into Fab alpha and (Fc alpha)2.SC fragments. The susceptibility of chimpanzee SIgA to IgA1 protease of a human pathogen could serve as the basis of an animal model to determine the importance of IgA1 protease in pathogenesis.
由人类黏膜病原体合成的免疫球蛋白(Ig)A蛋白酶对人类IgA具有独特的特异性,不会切割来自其他物种的IgA。相比之下,尚未有可靠证据表明动物病原体能够切割它们所感染动物的IgA。缺乏动物模型阻碍了人们对IgA1蛋白酶作为毒力因子重要性的理解。开发动物模型的一种策略是鉴定一种能够被产生人类IgA的病原体感染的物种,该物种的IgA易被该细菌的IgA1蛋白酶切割。黑猩猩可被流感嗜血杆菌感染,且在免疫学上与人类密切相关。基于这些原因,人们试图确定黑猩猩分泌型IgA(SIgA)是否易被流感嗜血杆菌的IgA1蛋白酶切割。本报告表明,黑猩猩SIgA确实可被流感嗜血杆菌IgA1蛋白酶在铰链区切割成Fabα和(Fcα)2.SC片段。黑猩猩SIgA对人类病原体IgA1蛋白酶的敏感性可作为一种动物模型的基础,用于确定IgA1蛋白酶在发病机制中的重要性。