Grunwald U, Fan X, Jack R S, Workalemahu G, Kallies A, Stelter F, Schütt C
Institute of Immunology and Transfusion Medicine, Greifswald, Germany.
J Immunol. 1996 Nov 1;157(9):4119-25.
Phagocytosis of bacteria by monocytes and neutrophil granulocytes provides an important first line of defense against bacterial infections. Opsonization of bacteria with complement and phagocytosis by neutrophils is dependent on divalent cations and does not take place in blood that has been anticoagulated with EDTA. Monocytes, however, do carry out phagocytosis even in the presence of EDTA. We show here that this divalent cation-independent phagocytosis pathway requires the presence of the LPS receptor CD14 on the cell surface. This pathway is dependent on the availability of LPS binding protein, can be blocked by anti-CD14 Abs, by an excess of soluble CD14, by excess free LPS, or by an excess of unlabeled Gram-negative bacteria. In contrast, intact Gram-positive bacteria fail to inhibit this process. These experiments define a CD14-dependent phagocytosis pathway for Gram-negative bacteria that operates in monocytes in human whole blood. This pathway may be able to deal with bacterial pathogens that have developed resistance to complement-dependent opsonization and phagocytosis by neutrophils.
单核细胞和中性粒细胞对细菌的吞噬作用为抵御细菌感染提供了重要的第一道防线。补体对细菌的调理作用以及中性粒细胞的吞噬作用依赖于二价阳离子，在用乙二胺四乙酸（EDTA）抗凝的血液中不会发生。然而，即使在存在EDTA的情况下，单核细胞也能进行吞噬作用。我们在此表明，这种不依赖二价阳离子的吞噬途径需要细胞表面存在脂多糖（LPS）受体CD14。该途径依赖于LPS结合蛋白的可用性，可被抗CD14抗体、过量的可溶性CD14、过量的游离LPS或过量的未标记革兰氏阴性菌阻断。相反，完整的革兰氏阳性菌无法抑制这一过程。这些实验确定了一种在人全血单核细胞中起作用的针对革兰氏阴性菌的CD14依赖性吞噬途径。该途径可能能够应对已对补体依赖性调理作用和中性粒细胞吞噬作用产生抗性的细菌病原体。
