Ezekowitz R A, Sim R B, MacPherson G G, Gordon S
J Clin Invest. 1985 Dec;76(6):2368-76. doi: 10.1172/JCI112249.
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 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.
巨噬细胞在没有外源性补体的情况下，通过与甘露糖基 - 岩藻糖基末端糖缀合物的凝集素样受体协同作用或单独作用的iC3b受体（3型补体受体）摄取酵母聚糖。我们之前提供的证据表明，巨噬细胞自身分泌能够在局部调理酵母聚糖的补体替代途径成分（Ezekowitz等人，《实验医学杂志》，1984年。159:244 - 260）。我们在此表明，在无血清条件下，共价结合的C3裂解产物C3b和iC3b可从与36小时贴壁培养的人单核细胞共同培养的酵母聚糖颗粒上洗脱下来。3型补体受体的配体结合位点参与巨噬细胞与酵母聚糖的相互作用，这通过用抗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得以证明。相比之下，结合与结合位点不同的受体表位的抗体IB4并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。人类多形核白细胞表达补体受体，但未知其分泌补体蛋白，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7天贴壁培养的人巨噬细胞中是呼吸爆发活性的较弱触发剂，但当这些细胞在无血清培养基中共同培养并用酵母聚糖刺激时，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/或其他产物可能在能够激活替代途径的病原体的调理和裂解中发挥重要作用，并在一线宿主防御中介导巨噬细胞 - 中性粒细胞协作。
