Horwitz M A, Silverstein S C
J Clin Invest. 1980 Jan;65(1):82-94. doi: 10.1172/JCI109663.
To define mechanisms by which polysaccharide capsules confer enhanced virulence on gram-negative bacteria, we examined the effect of the Escherichia coli capsule on complement fixation to the bacterial surface and on phagocytosis and killing of these bacteria by mouse macrophages and human polymorphonuclear leukocytes (PMN) and monocytes. When E. coli were attached to mouse macrophages with concanavalin A, the macrophages readily phagocytosed unencapsulated but not encapsulated bacteria even in the presence of fresh mouse serum; macrophages did not phagocytose encapsulated E. coli unless antibacterial or anti-Con A antibody was added. Similarly, when these bacteria were attached to human PMN with Con A, PMN ingested unencapsulated but not encapsulated E. coli. PMN phagocytosed and killed encapsulated serum-resistant E. coli only in the presence of both complement and antibacterial antibody; PMN phagocytosed and killed unencapsulated E. coli of the same strain in the presence of complement alone. Fluorescence microscopy showed that antibody had to be present for encapsulated but not unencapsulated E. coli to fix complement to its surface. To examine the role of the complement receptors of human PMN and monocytes in phagocytosis and killing of encapsulated E. coli, we used human and rabbit antibacterial immunoglobulin (Ig)M to fix complement to the bacteria. PMN and monocytes phagocytosed and killed encapsulated E. coli in the presence of both IgM and complement, but not in the presence of either serum opsonin alone. In the presence of antibacterial IgG, PMN and monocytes required complement to effectively phagocytose and kill the E. coli. We conclude that (a) attachment by itself results in ingestion of unencapsulated but not encapsulated E. coli; (b) under physiologic conditions, E. coli are not phagocytosed or killed the absence of antibody, the E. coli capsule blocks complement fixation to the bacterial surface probably by masking surface components, such as lipopolysaccharide, capable of activating the complement pathway; (d) the E. coli capsule imposes a requirement for specific antibacterial antibody for complement fixation; and (e) the complement receptor of human PMN and monocytes mediates phagocytoses of complement-coated encapsulated bacteria and is the primary mediator of phagocytosis and killing of these bacteria.
为了确定多糖荚膜赋予革兰氏阴性菌更强毒力的机制，我们研究了大肠杆菌荚膜对补体固定于细菌表面的影响，以及小鼠巨噬细胞、人类多形核白细胞（PMN）和单核细胞对这些细菌的吞噬和杀伤作用。当用伴刀豆球蛋白A将大肠杆菌附着于小鼠巨噬细胞时，即使存在新鲜的小鼠血清，巨噬细胞也能轻易吞噬未被包裹的细菌，但不能吞噬被包裹的细菌；除非添加抗菌或抗伴刀豆球蛋白A抗体，巨噬细胞才会吞噬被包裹的大肠杆菌。同样，当用伴刀豆球蛋白A将这些细菌附着于人类PMN时，PMN会摄取未被包裹的大肠杆菌，而不会摄取被包裹的大肠杆菌。PMN只有在补体和抗菌抗体同时存在的情况下，才会吞噬并杀死具有血清抗性的被包裹大肠杆菌；而PMN在仅存在补体的情况下，就能吞噬并杀死同一菌株的未被包裹的大肠杆菌。荧光显微镜检查显示，对于被包裹的大肠杆菌，必须存在抗体才能使其表面固定补体，而未被包裹的大肠杆菌则无需抗体。为了研究人类PMN和单核细胞的补体受体在吞噬和杀伤被包裹的大肠杆菌中的作用，我们使用人类和兔抗菌免疫球蛋白（Ig）M使补体固定于细菌。PMN和单核细胞在IgM和补体同时存在的情况下，会吞噬并杀死被包裹的大肠杆菌，但在单独存在任何一种血清调理素时则不会。在存在抗菌IgG的情况下，PMN和单核细胞需要补体才能有效地吞噬并杀死大肠杆菌。我们得出以下结论：（a）仅附着本身会导致未被包裹的大肠杆菌被摄取，但不会导致被包裹的大肠杆菌被摄取；（b）在生理条件下，没有抗体时，大肠杆菌不会被吞噬或杀死，大肠杆菌荚膜可能通过掩盖能够激活补体途径的表面成分（如脂多糖）来阻止补体固定于细菌表面；（d）大肠杆菌荚膜要求存在特异性抗菌抗体才能进行补体固定；（e）人类PMN和单核细胞的补体受体介导对补体包被的被包裹细菌的吞噬作用，并且是吞噬和杀伤这些细菌的主要介质。
