Macrophage complement and lectin-like receptors bind Leishmania in the absence of serum.
Macrophage complement and lectin-like receptors bind Leishmania in the absence of serum.
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DOI：
10.1084/jem.162.1.324
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发表时间：
1985-07-01
期刊：
影响因子：
--
通讯作者：
Gordon S
中科院分区：
文献类型：
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作者：
Blackwell JM;Ezekowitz RA;Roberts MB;Channon JY;Sim RB;Gordon S
我们研究了巨噬细胞（Mφ）对裂解的第三补体成分（iC3b，CR3）的质膜受体以及甘露糖基/岩藻糖基受体（MFR）在杜氏利什曼原虫结合和摄取中的相对作用。在没有外源性补体的情况下，前鞭毛体（替代补体途径的良好激活剂）的结合和摄取受到抗CR3单克隆抗体M1/70、抗C3抗体的Fab部分或亲核试剂水杨羟肟酸钠（一种C3固定抑制剂）的抑制。这有力地证明了存在于前鞭毛体表面的巨噬细胞衍生的裂解C3（iC3b）介导了与CR3的结合。使用MFR活性的可溶性抑制剂甘露聚糖或核糖核酸酶B也观察到对前鞭毛体结合和摄取的同等抑制作用。同时阻断这两种巨噬细胞受体未观察到累加效应。对于无鞭毛体（替代途径的弱激活剂），观察到三种CR3介导结合的可溶性抑制剂与两种MFR介导结合的可溶性抑制剂具有较小但相当的作用。在使CR3或MFR无法接近的调节实验中表明，这两种受体必须存在于寄生虫所结合的巨噬细胞膜区段上。这两种不同的巨噬细胞受体的联合功能可能为识别和摄取已知能激活替代途径的其他致病性原虫提供一种通用机制。
We have examined the relative roles of the macrophage (M phi) plasma membrane receptor for the cleaved third complement component (iC3b, CR3) and of the mannosyl/fucosyl receptor (MFR) in binding and ingestion of Leishmania donovani. In the absence of exogenous complement, the binding and ingestion of promastigotes, which are good activators of the alternative complement pathway, were inhibited by the anti-CR3 monoclonal antibody M1/70, by the Fab portion of an anti-C3 antibody, or by the nucleophile, sodium salicyl hydroxamate, an inhibitor of C3 fixation. This provides strong evidence that M phi- derived, cleaved C3 (iC3b) present on the promastigote surface mediates binding to CR3. Equivalent inhibition of promastigote binding and ingestion was also observed using the soluble inhibitors of MFR activity, mannan or ribonuclease B. No additive effect for blocking the two M phi receptors simultaneously was observed. For amastigotes, which are poor activators of the alternative pathway, a lesser but nevertheless equivalent effect was observed for the three soluble inhibitors of CR3-mediated binding vs. the two soluble inhibitors of MFR-mediated binding. Modulation experiments in which either CR3 or MFR had been rendered inaccessible demonstrated that both receptors must be present on the segment of M phi membrane to which the parasite binds. The combined function of these two distinct M phi receptors may provide a general mechanism for recognition and ingestion of other pathogenic protozoa known to activate the alternative pathway.