Schlesinger L S, Bellinger-Kawahara C G, Payne N R, Horwitz M A
Department of Medicine, UCLA School of Medicine 90024.
J Immunol. 1990 Apr 1;144(7):2771-80.
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.
我们研究了人类单核细胞对有毒力结核分枝杆菌的受体-配体相互作用及吞噬方法。抗补体受体（CR）的单克隆抗体（mAb）可抑制新鲜非免疫血清中结核分枝杆菌的黏附和吞噬。一种抗1型CR（CR1）的mAb可使结核分枝杆菌的黏附抑制40±5%，三种不同的抗3型CR（CR3）的mAb各自可使黏附抑制39±5%至47±4%。一种抗CR1的mAb与三种抗CR3的mAb之一联合使用时，可使黏附抑制高达64±7%。最显著的是，两种联合使用的抗CR3的mAb可使黏附抑制高达81±2%。抗其他单核细胞表面抗原的mAb对黏附无显著影响。同样，在热灭活血清存在的情况下，抗CR而非其他单核细胞表面抗原的mAb可抑制调理过的结核分枝杆菌的黏附。通过电子显微镜观察，单核细胞摄取在非免疫血清存在下黏附的所有结核分枝杆菌；抗CR3的mAb可显著抑制摄取。与CR不同，Fc受体和酵母聚糖的β-葡聚糖可抑制性受体在介导结核分枝杆菌的黏附或摄取中作用很小或无作用。结核分枝杆菌的黏附依赖血清，最佳黏附需要血清浓度大于或等于2.5%。血清热灭活可显著降低结核分枝杆菌的黏附（75.5±7%），细菌的预调理可使黏附增强2.9±0.4倍。在C3或B因子缺失的血清中黏附也显著降低；补充C3或B因子可使黏附分别增加2.1±0.4倍和1.86±0.05倍。Fab抗C3 IgG可显著抑制调理过的结核分枝杆菌的单核细胞黏附（71±1%）。通过全细菌细胞酶联免疫吸附测定法确定，C3成分通过替代补体途径固定于结核分枝杆菌。从电子显微镜观察来看，人类单核细胞通过传统吞噬作用摄取结核分枝杆菌。本研究表明，人类单核细胞CR1和CR3介导结核分枝杆菌的吞噬作用，血清中的C3成分作为主要的细菌结合配体发挥作用。
