MACROPHAGES HAVE CELL-SURFACE IL-10 THAT REGULATES MACROPHAGE BACTERICIDAL ACTIVITY

IL-10, which is secreted by multiple cell types, has regulatory effect s on macrophages, including decreasing their ability to kill some micr oorganisms. The experiments presented here test the hypothesis that en dogenous IL-10 inhibits the ability of macrophages to kill the faculta tive intracellular bacterium, Listeria monocytogenes. We show that the nonbactericidal macrophage hybrid, H36.12j (12j), can kill Listeria a fter incubation for 3 days with anti-IL-10 mAb. IL-10 was not detected in 12j macrophage supernatants by ELISA. However, flow cytometric ana lysis revealed high levels of IL-10 on the 12j cell surface, This indi cates that macrophages that fail to secrete IL-10 may express IL-10 on the cell surface, and this IL-10 appears to suppress listericidal act ivity, Surface IL-10 is not unique to the 12j macrophage hybrid and ma y correlate with the absence of bactericidal activity in other macroph ages, For instance, nonlistericidal resident and thioglycolate-elicite d 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 b ecome bactericidal, the surface IL-10 is biologically active, and it a ppears to regulate macrophage bactericidal activity.