MACROPHAGE STIMULATION BY BACTERIAL LIPOPOLYSACCHARIDES .3. SELECTIVE UNRESPONSIVENESS OF C3H-HEJ MACROPHAGES TO THE LIPID-A DIFFERENTIATION SIGNAL

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  • 1 January 1979
    • journal article
    • research article
    • Vol. 123  (5) , 2304-2310
Abstract
Peritoneal macrophages from the endotoxin-unresponsive C3H/HeJ substrain of mice were entirely refractory to activation in vitro by protein-free LPS [Escherichia coli lipopolysaccharide], a defect that was not overcome by co-culture of spleen cells from the responder C3H/St substrain with LPS resistant C3H/HeJ macrophages. The defect in responsiveness appears confined to the lipid A activation signal since C3H/HeJ macrophages were fully activated after in vitro treatment by lipid A protein (LAP).sbd.LPS complex, isolated LAP and BCG. After exposure to allogeneic tumor cells in vivo, C3H/HeJ macrophages were cytotoxic for tumor target cells in vitro. Macrophages from the responder C3H/St strain were fully activated by protein-free LPS to become cytolytic for tumor cells in vitro. C3H/HeJ macrophages, therefore, exhibit a highly selective defect characterized by unresponsiveness to the lipid A activation signal of protein-free LPS and resistance to the toxic effects of high concentrations of LPS that were lethal to the responder C3H/St strain.