Lipopolysaccharide and polyribonucleotide activation of macrophages: implications for a natural triggering signal in tumor cell killing.
There is evidence that activation of macrophages for tumor cell killing can involve either two signals (interferon/lipopolysaccharide, for example) or one signal (lipopolysaccharide or double-stranded RNA, for example). We investigated the apparent one-signal activation of bone marrow-derived macrophages for P815 mastocytoma killing by treatment with lipopolysaccharide (LPS) or by the synthetic double-stranded polyribonucleotide polyinosinic acid-polycytidylic acid (poly I:C). We found that "direct" activation of macrophages by either LPS or poly I:C was still a two-signal process. Based on antibody neutralizations, the first signal was probably mediated by LPS or poly I:C induced alpha/beta interferon in the macrophage cultures, and the second signal was that of a direct effect of the LPS or poly I:C on the cell. The fact that poly I:C can provide the triggering signal for macrophage activation suggests a possible role for double-stranded RNA structures in macrophage triggering. Such double-stranded RNA requirements could be met by single-stranded RNAs that possess significant double-strandedness in their structures.
D000818:Animals; D000906:Antibodies / Q000502:physiology; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D007370:Interferon Type I / Q000276:immunology / Q000502:physiology; D007371:Interferon-gamma / Q000276:immunology / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D012515:Mast-Cell Sarcoma / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D011070:Poly I-C / Q000494:pharmacology*; D012330:RNA, Double-Stranded / Q000502:physiology
D000906:Antibodies; D007370:Interferon Type I; D008070:Lipopolysaccharides; D012330:RNA, Double-Stranded; D007371:Interferon-gamma; D011070:Poly I-C