Drevets D A, Leenen P J, Campbell P A
Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado, USA.
Cell Immunol. 1996 Apr 10;169(1):1-6. doi: 10.1006/cimm.1996.0083.
Previous work demonstrated that engagement of complement receptor type 3 (CR3) was required for inflammatory peritoneal macrophages to phagocytose and kill the facultative intracellular bacterium Listeria monocytogenes. The experiments described here tested the role of CR3 in phagocytosis and killing of Listeria by a clonal population of TNF-alpha/IFN-gamma-stimulated macrophage precursor hybrids. Stimulation with TNF-alpha and IFN-gamma increased CR3 expression 20-fold and induced a big increase in phagocytic activity. Phagocytosis and killing of Listeria by these cells were inhibited when bacteria were opsonized with complement-depleted serum or by incubation of the macrophages with anti-CR3 mAb. Furthermore, cytokine-stimulated macrophages could not kill Listeria opsonized with heat-inactivated anti-Listeria antiserum, indicating that macrophage receptors which mediate phagocytosis do not necessarily promote bactericidal activity. These data suggest that upregulation of CR3 and CR3-mediated phagocytosis are mechanisms by which TNF-alpha and IFN-gamma stimulate nonphagocytic, nonbactericidal macrophage precursors to kill intracellular bacterial pathogens.
先前的研究表明，炎性腹膜巨噬细胞吞噬并杀死兼性细胞内细菌单核细胞增生李斯特菌需要补体受体3（CR3）的参与。本文所述实验测试了CR3在肿瘤坏死因子-α/干扰素-γ刺激的巨噬细胞前体杂交克隆群体吞噬和杀死李斯特菌中的作用。用肿瘤坏死因子-α和干扰素-γ刺激可使CR3表达增加20倍，并导致吞噬活性大幅增加。当用补体缺失血清调理细菌或用抗CR3单克隆抗体孵育巨噬细胞时，这些细胞对李斯特菌的吞噬和杀伤作用受到抑制。此外，细胞因子刺激的巨噬细胞无法杀死用热灭活抗李斯特菌抗血清调理的李斯特菌，这表明介导吞噬作用的巨噬细胞受体不一定能促进杀菌活性。这些数据表明，CR3的上调和CR3介导的吞噬作用是肿瘤坏死因子-α和干扰素-γ刺激非吞噬性、非杀菌性巨噬细胞前体杀死细胞内细菌病原体的机制。
