Defective tumoricidal capacity of macrophages from P/J mice: characterization of the macrophage cytotoxic defect after in vivo and in vitro activation stimuli.
Unlike macrophages from responsive mouse strains, peritoneal cells of P/J mice treated in vivo with viable Mycobacterium bovis, strain BCG, or killed Corynebacterium parvum fail to develop tumoricidal activity. P/J macrophages treated in vitro with lymphokine-rich supernatants, bacterial endotoxic lipopolysaccharides (LPS) or T cell mitogens also fail to develop cytotoxic activity. Experimental manipulation of effector:target cell ratios, doses of activation stimuli, or tumor target cells did not evoke cytotoxic activity. The macrophage defect of P/J mice appeared similar to that of lipid A-insensitive C3H/HeJ mice. The macrophage defect of C3H/HeJ mice is controlled by a gene identical or closely linked to the Lpsd gene. Tumoricidal defects of P/J macrophages, however, appeared independent of the Lpsd gene: responses of P/J spleen cells or macrophages to LPS, which are controlled by the Lps gene, were normal. P/J mice therefore represent a distinct and potentially useful genetic probe for characterization of mechanisms in macrophage activation.
D000818:Animals; D002633:Chemotaxis; D003602:Cytotoxicity, Immunologic; D007249:Inflammation / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008222:Lymphokines / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D009163:Mycobacterium bovis / Q000276:immunology; D010587:Phagocytosis; D011425:Propionibacterium acnes / Q000276:immunology
D008070:Lipopolysaccharides; D008222:Lymphokines