Macrophage-produced IL-12p70 mediates hemorrhage-induced damage in a complement-dependent manner.
Hemorrhage and hemorrhagic shock instigate intestinal damage and inflammation. Multiple components of the innate immune response, including complement and neutrophil infiltration, are implicated in this pathology. To investigate the interaction of complement activation and other components of the innate immune response during hemorrhage, we treated mice after hemorrhage with CR2-fH, a targeted inhibitor of the alternative complement pathway and assessed intestinal damage and inflammation 2 h after hemorrhage. In wild-type mice, CR2-fH attenuated hemorrhage-induced, midjejunal damage and inflammation as determined by decreased mucosal damage, macrophage infiltration, leukotriene B4, IL-12p40, and TNF-[alpha] production. The critical nature of intestinal macrophage infiltration and activation in the response to hemorrhage was further determined using mice pretreated with clodronate-containing liposomes. The absence of either macrophages or IL-12p70 attenuated intestinal damage. These data suggest that complement activation and macrophage infiltration with IL-12p70 production are critical to hemorrhage-induced midjejunal damage and inflammation.
Hylton
Diana J
DJ
Division of Biology, Kansas State University, Manhattan, KS 66506, USA.
Hoffman
Sara M
SM
Van Rooijen
N
N
Tomlinson
Stephen
S
Fleming
Sherry D
SD
D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology; D004002:Clodronic Acid / Q000494:pharmacology; D003167:Complement Activation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D051056:Complement Inactivating Agents / Q000494:pharmacology; D003165:Complement System Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007113:Immunity, Innate / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D007410:Intestinal Diseases / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000276:immunology; D007975:Leukotriene B4 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D008262:Macrophage Activation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D012771:Shock, Hemorrhagic / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology
D050071:Bone Density Conservation Agents; D051056:Complement Inactivating Agents; D014409:Tumor Necrosis Factor-alpha; D004002:Clodronic Acid; D018664:Interleukin-12; D007975:Leukotriene B4; D003165:Complement System Proteins