Phagocytosis of Mycobacterium tuberculosis is mediated by human monocyte complement receptors and complement component C3.
Phagocytosis of Mycobacterium tuberculosis is mediated by human monocyte complement receptors and complement component C3.
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DOI：
10.4049/jimmunol.144.7.2771
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发表时间：
1990-04
影响因子：
4.4
通讯作者：
L. Schlesinger;C. Bellinger-Kawahara;N. Payne;M. Horwitz
中科院分区：
文献类型：
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作者：
L. Schlesinger;C. Bellinger-Kawahara;N. Payne;M. Horwitz
我们研究了受体-配体相互作用和人单核细胞吞噬毒性结核分枝杆菌的方法。抗补体受体（CR）单克隆抗体抑制M.新鲜非免疫血清中的结核病。抗1型CR（CR 1）的mAb可抑制M的粘附。三种不同的抗3型CR（CR 3）mAb分别抑制39 +/-5%至47 +/-4%的粘附。抗CR 1 mAb与三种抗CR 3 mAb之一联合使用可抑制高达64 +/-7%的粘附。最引人注目的是，组合使用的两种抗CR 3的mAb抑制粘附高达81 +/-2%。抗其他单核细胞表面抗原的mAb对粘附无显著影响。以类似的方式，针对CR而不是其他单核细胞表面Ag的mAb抑制预调理的M的粘附。在热灭活血清存在下的结核病。通过电子显微镜，单核细胞摄取所有M。结核病，坚持在非免疫血清的存在下;单克隆抗体对CR 3显着抑制摄入。与CR相反，FcR和酵母聚糖的β-葡聚糖可降解受体在介导M.结核粘附或摄入。坚持M。结核病是血清依赖性的，需要大于或等于2.5%的血清以获得最佳的粘附。热灭活血清可明显降低M.结核病（75.5 +/- 7%）和细菌的预调理作用使粘附增强2.9 +/- 0.4倍。在C3或因子B耗尽的血清中，粘附性也显著降低;补充C3或因子B分别使粘附性增加2.1 +/- 0.4倍和1.86 +/- 0.05倍。Fab anti-C3 IgG显著抑制M.结核病（71 +/- 1%）。C分量C3固定到M。通过全细菌细胞ELISA测定，通过替代C途径抑制结核病。人单核细胞摄取M.通过电子显微镜观察到的常规吞噬作用引起的结核病。本研究表明，人单核细胞CR 1和CR 3介导M.血清中的C组分C3是主要的细菌结合配体。
We have examined the receptor-ligand interactions and the method of phagocytosis of virulent Mycobacterium tuberculosis by human monocytes. mAb against complement receptors (CR) inhibit adherence and phagocytosis of M. tuberculosis in fresh nonimmune serum. A mAb against the type 1 CR (CR1) inhibits adherence of M. tuberculosis by 40 +/- 5%, and three different mAb against the type 3 CR (CR3) each inhibit adherence by 39 +/- 5% to 47 +/- 4%. A mAb against CR1 used in combination with one of the three mAb against CR3 inhibits adherence by up to 64 +/- 7%. Most strikingly, two mAb used in combination against CR3 inhibit adherence by up to 81 +/- 2%. mAb against other monocyte surface Ag do not significantly influence adherence. In like fashion, mAb against CR but not other monocyte surface Ag inhibit adherence of preopsonized M. tuberculosis in the presence of heat-inactivated serum. By electron microscopy, monocytes ingest all M. tuberculosis that adhere in the presence of nonimmune serum; mAb against CR3 markedly inhibit ingestion. In contrast to CR, the FcR and the beta-glucan-inhibitable receptor for zymosan play little or no role in mediating M. tuberculosis adherence or ingestion. Adherence of M. tuberculosis is serum-dependent, requiring greater than or equal to 2.5% serum for optimal adherence. Heat inactivation of serum markedly reduces adherence of M. tuberculosis (75.5 +/- 7%) and preopsonization of bacteria enhances adherence by 2.9 +/- 0.4-fold. Adherence is also markedly reduced in C3- or factor B-depleted serum; repletion with C3 or factor B increases adherence by 2.1 +/- 0.4-fold and 1.86 +/- 0.05-fold, respectively. Fab anti-C3 IgG markedly inhibits monocyte adherence of preopsonized M. tuberculosis (71 +/- 1%). C component C3 is fixed to M. tuberculosis by the alternative C pathway as determined by a whole bacterial cell ELISA. Human monocytes ingest M. tuberculosis by conventional phagocytosis as viewed by electron microscopy. This study demonstrates that human monocyte CR1 and CR3 mediate phagocytosis of M. tuberculosis and C component C3 in serum is acting as the major bacterium-bound ligand.