Macrophages have cell surface IL-10 that regulates macrophage bactericidal activity.
IL-10, which is secreted by multiple cell types, has regulatory effects on macrophages, including decreasing their ability to kill some microorganisms. The experiments presented here test the hypothesis that endogenous IL-10 inhibits the ability of macrophages to kill the facultative intracellular bacterium, Listeria monocytogenes. We show that the nonbactericidal macrophage hybrid, H36.12j (12j), can kill Listeria after incubation for 3 days with anti-IL-10 mAb. IL-10 was not detected in 12j macrophage supernatants by ELISA. However, flow cytometric analysis revealed high levels of IL-10 on the 12j cell surface. This indicates that macrophages that fail to secrete IL-10 may express IL-10 on the cell surface, and this IL-10 appears to suppress listericidal activity. Surface IL-10 is not unique to the 12j macrophage hybrid and may correlate with the absence of bactericidal activity in other macrophages. For instance, nonlistericidal resident and thioglycolate-elicited peritoneal exudate cells have 24 to 72% IL-10-positive macrophages. In contrast listericidal proteose peptone-elicited peritoneal exudate cells contained < 5% IL-10-positive macrophages. Whether this IL-10 is an integral membrane protein or is bound to IL-10 receptors is not yet known. However, the IL-10 does not elute with acid as other passively bound molecules do, nor does exogenous IL-10 bind to macrophages. In either case, since anti-IL-10 induces nonbactericidal macrophages to become bactericidal, the surface IL-10 is biologically active, and it appears to regulate macrophage bactericidal activity.
Fleming
S D
SD
Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206, USA.
Campbell
P A
PA
D000818:Animals; D000891:Anti-Infective Agents, Local / Q000032:analysis*; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002460:Cell Line; D005260:Female; D016753:Interleukin-10 / Q000276:immunology / Q000502:physiology*; D008089:Listeria monocytogenes / Q000276:immunology; D008262:Macrophage Activation; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000382:microbiology; D008565:Membrane Proteins / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010587:Phagocytosis / Q000187:drug effects*; D018123:Receptors, Interleukin / Q000276:immunology; D053701:Receptors, Interleukin-10
D000891:Anti-Infective Agents, Local; D000911:Antibodies, Monoclonal; D008565:Membrane Proteins; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D016753:Interleukin-10