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.