Mechanism of action of macrophage-derived suppressor factor produced by soluble immune response suppressor-treated macrophages.
After a 2-hr incubation with soluble immune response suppressor (SIRS), a product of concanavalin A-activated murine T cells, macrophages release a factor, M phi-derived suppressor factor (M phi-SF), which nonspecifically suppresses immune responses in vitro. The mechanism(s) of action of M phi-SF and range of cell types affected by M phi-SF have been investigated. M phi-SF suppressed antibody responses to background levels if added at culture initiation and by 80 to 90% if added as late as 2 hr before assay. Primary and secondary IgM and IgG antibody responses, proliferative responses to T cell and B cell mitogens, antibody and protein secretion, and the division of several tumor cell lines in culture were inhibited by M phi-SF. Division of synchronized tumor cells was inhibited when M phi-SF was added at any point prior to and during mitosis; this inhibition could be reversed with 2-mercaptoethanol. In the presence of M phi-SF, asynchronous tumor cells accumulated in the cell cycle just prior to cell division and could be released into mitosis by 2-mercaptoethanol. These data indicate that M phi-SF inhibits cell division by causing a block at or in mitosis and suggest that M phi-SF may be a general inhibitor of cellular proliferation and possibly of protein secretion.
D000818:Animals; D000917:Antibody Formation; D000921:Antibody-Producing Cells / Q000276:immunology; D002453:Cell Cycle; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D006462:Hemolytic Plaque Technique; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009930:Organic Chemicals; D012995:Solubility; D013997:Time Factors
D007166:Immunosuppressive Agents; D009930:Organic Chemicals; C023051:suppressive factor of allergy; D004247:DNA