Incorporation of bacterial lipopolysaccharide by human Leu-11a+ natural killer cells. Ultrastructural and functional correlations.
Lipopolysaccharides (LPS) of gram-negative bacteria are known to augment the ability of macrophages and natural killer (NK) cells to lyse susceptible target cells. In the present studies, we sought correlations between the ultrastructural changes and function of Leu-11a+ cells from the peripheral blood mononuclear cells which occurred as a result of their incorporation of LPS. We also studied the effect of LPS on the NK activity of purified Leu-11a+ cells. LPS samples from E. coli and Pseudomonas aeruginosa were utilized. A double-immunolabeling technique employing immunogold and immunoperoxidase markers was used to identify the Leu-11a+ cells with incorporated LPS. Pinocytosis, phagocytosis, and direct insertion into membrane bilayers appeared to be the routes for incorporation of LPS by Leu-11a+ cells. Subsequent ultrastructural effects included dilation of intracellular membrane compartments, formation of tubuloreticular inclusions and increased acid phosphatase activity. Opsonized Staphylococcus aureus were ingested both by control and LPS-treated Leu-11a+ cells; however, the number of Leu-11a+ cells with bacteria increased significantly as a result of LPS treatment. Autoradiography combined with immunolabeling showed no [3H] thymidine incorporation by either control or LPS-stimulated Leu-11a+ cells. NK cell-mediated cytotoxicity was significantly increased as compared with the control (p less than or equal to 0.02) when isolated Leu-11a+ cells were treated with LPS for 24 hours. This result suggests that LPS may have direct effect on the NK cell activity. Tests of peripheral blood mononuclear cell samples after LPS treatment showed up to a 2-fold increase in NK cytotoxicity and a dose-related increase of in vitro interferon production. This latter finding together with the ultrastructural observations of tubuloreticular inclusions in Leu-11a+ cells suggests that, in addition to any direct effect of LPS, cytotoxic activity could be indirectly augmented as a result of autocrine or paracrine interferon, or lymphokine production.
D000135:Acid Phosphatase / Q000378:metabolism; D002455:Cell Division; D003602:Cytotoxicity, Immunologic; D004926:Escherichia coli; D006801:Humans; D007150:Immunohistochemistry; D007372:Interferons / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D008070:Lipopolysaccharides / Q000378:metabolism* / Q000494:pharmacology; D008854:Microscopy, Electron; D010587:Phagocytosis / Q000187:drug effects; D010873:Pinocytosis; D011550:Pseudomonas aeruginosa; D013936:Thymidine / Q000378:metabolism
D008070:Lipopolysaccharides; D007372:Interferons; D000135:Acid Phosphatase; D013936:Thymidine