SOLUBLE HUMAN-COMPLEMENT RECEPTOR-TYPE-1 INHIBITS COMPLEMENT-MEDIATED HOST-DEFENSE
SOLUBLE HUMAN-COMPLEMENT RECEPTOR-TYPE-1 INHIBITS COMPLEMENT-MEDIATED HOST-DEFENSE
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DOI：
10.1128/cdli.1.5.585-589.1994
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发表时间：
1994-09-01
期刊：
影响因子：
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通讯作者：
WINKELSTEIN, JA
中科院分区：
文献类型：
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作者：
SWIFT, AJ;COLLINS, TS;WINKELSTEIN, JA
可溶性补体受体1型（sCR1）是补体激活的强效抑制剂。由于这种能力，sCR 1可能被证明是一种重要的治疗剂，可用于阻断各种临床显著疾病中不受控制的补体激活的免疫病理学效应。虽然之前的几项研究已经检测了sCR1抑制补体介导的免疫病理损伤的能力，但没有关于其干扰宿主对感染的防御能力的信息。在目前的实验中，sCR 1在体外对人多形核白细胞对肺炎链球菌的吞噬作用产生浓度依赖性抑制作用。sCR1不仅抑制肺炎球菌的补体依赖性调理作用，而且在更高浓度下，它还抑制先前已被调理的细菌的摄入。此外，当大鼠注射sCR 1时，它以剂量依赖性方式抑制其血清溶血活性和血清调理素活性。最后，对于用sCR 1处理的大鼠，在用S.肺炎假单胞菌和铜绿假单胞菌。这些数据表明，sCR1显着抑制补体介导的宿主防御细菌感染。
Soluble complement receptor type 1 (sCR1) is a powerful inhibitor of complement activation. Because of this ability, sCR1 may prove to be an important therapeutic agent that can be used to block the immunopathologic effects of uncontrolled complement activation in a variety of clinically significant disorders. Although several previous studies have examined the ability of sCR1 to inhibit complement-mediated immunopathologic damage, there is no information on its ability to interfere with the host's defense against infection. In the current experiments sCR1 exerted a concentration-dependent inhibitory effect on the phagocytosis of Strepto-coccus pneumoniae by human polymorphonuclear leukocytes in vitro. Not only did sCR1 inhibit complement-dependent opsonization of the pneumococcus but a higher concentrations it also inhibited the ingestion of bacteria which had been previously opsonized. Furthermore, when rats were injected with sCR1, it inhibited both their serum hemolytic activity and serum opsonic activity in a dose-dependent fashion. Finally, for rats treated with sCR1, the 50% lethal dose was also shown to be significantly lower than that for control animals after intravenous challenge with S. pneumoniae and Pseudomonas aeruginosa. These data demonstrate that sCR1 significantly inhibits complement-mediated host defense against bacterial infection.