INTERACTION OF HUMAN-MONOCYTES, MACROPHAGES, AND POLYMORPHONUCLEAR LEUKOCYTES WITH ZYMOSAN INVITRO - ROLE OF TYPE-3 COMPLEMENT RECEPTORS AND MACROPHAGE-DERIVED COMPLEMENT
INTERACTION OF HUMAN-MONOCYTES, MACROPHAGES, AND POLYMORPHONUCLEAR LEUKOCYTES WITH ZYMOSAN INVITRO - ROLE OF TYPE-3 COMPLEMENT RECEPTORS AND MACROPHAGE-DERIVED COMPLEMENT
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DOI：
10.1172/jci112249
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发表时间：
1985-12-01
影响因子：
15.9
通讯作者：
GORDON, S
中科院分区：
文献类型：
--
作者：
EZEKOWITZ, RAB;SIM, RB;GORDON, S
在没有外源性补体的情况下，巨噬细胞通过iC3b受体（3型补体受体）摄取酵母聚糖，此过程可与甘露糖基 - 岩藻糖基末端糖缀合物的凝集素样受体协同作用，也可单独发生。我们先前提供的证据表明，巨噬细胞自身可分泌补体替代途径的成分，能够在局部调理酵母聚糖（Ezekowitz等人，《实验医学杂志》1984年，159卷：244 - 260页）。在此我们表明，在无血清的情况下，从与贴壁36小时的人单核细胞共同培养的酵母聚糖颗粒中可洗脱共价结合的C3裂解产物C3b和iC3b。如通过抗C3抗体的Fab片段以及单克隆抗受体抗体M01和OKM10对酵母聚糖结合和摄取的抑制研究所示，3型补体受体的配体结合位点参与巨噬细胞 - 酵母聚糖的相互作用。相反，与不同于结合位点的受体表位结合的抗体IB4不抑制酵母聚糖的摄取。分别用抗补体受体抗体和富含甘露糖的酵母甘露聚糖对巨噬细胞受体进行选择性调节，证实补体受体和凝集素样受体是不同的。人多形核白细胞表达补体受体，但已知其不分泌补体蛋白，它们仅结合并摄取外源性调理的酵母聚糖。未调理的酵母聚糖在中性粒细胞或贴壁7天的人巨噬细胞中是呼吸爆发活性的弱触发剂，但当这些细胞在无血清培养基中共同培养并受到酵母聚糖刺激时，会诱导细胞聚集并分泌大量超氧阴离子。我们的研究表明，巨噬细胞在血管外部位合成的补体和/或其他产物在调理和裂解能够激活替代途径的病原体以及介导巨噬细胞 - 中性粒细胞在一线宿主防御中的协作方面可能发挥重要作用。
Macrophages take up zymosan in the absence of exogenous complement via receptors for iC3b (type 3 complement receptors) acting with or without lectin-like receptors for mannosyl-fucosyl-terminated glycoconjugates. We previously provided evidence that macrophages themselves secrete complement-alternative pathway components able to opsonize zymosan locally (Ezekowitz et al., J. Exp. Med. 1984. 159:244-260). We show here that covalently bound C3 cleavage products C3b and iC3b can be eluted from zymosan particles cultivated with 36-h adherent human monocytes in the absence of serum. The ligand binding site of type 3 complement receptors is involved in macrophage-zymosan interactions as shown by inhibition studies of zymosan binding and uptake with Fab fragments of anti-C3 antibodies and monoclonal antireceptor antibodies and monoclonal antireceptor antibodies M01 and OKM10. In contrast, antibody IB4, which binds to a receptor epitope distinct from the binding site, does not inhibit zymosan uptake. Selective modulation of macrophage receptors onto anticomplement receptor antibody and mannose-rich yeast mannan, respectively, confirms that the complement and lectin-like receptors are distinct. Human polymorphonuclear leukocytes, which express receptors for complement, but are not known to secrete complement proteins, bind and ingest only exogenously opsonized zymosan. Unopsonized zymosan is a poor trigger of respiratory burst activity in neutrophils or 7-d adherent human macrophages, but induces cell aggregation and secretion of large amounts of superoxide anion when these cells are co-cultivated in serum-free medium and challenged with zymosan. Our studies indicate that complement and/or other products synthesized by macrophages at extravascular sites could play an important role in opsonization and lysis of pathogens able to activate the alternative pathway and mediate macrophage-neutrophil collaboration in first-line host defence.