title: TLR2 modulates antibodies required for intestinal ischemia/reperfusion-induced damage and inflammation.
abstract: In multiple clinical conditions, including trauma and hemorrhage, reperfusion magnifies ischemic tissue damage. Ischemia induces expression of multiple neoantigens, including lipid alterations that are recognized by the serum protein, β2-glycoprotein I (β2-GPI). During reperfusion, binding of β2-GPI by naturally occurring Abs results in an excessive inflammatory response that may lead to death. As β2-GPI is critical for intestinal ischemia/reperfusion (IR)-induced tissue damage and TLR2 is one of the proposed receptors for β2-GPI, we hypothesized that IR-induced intestinal damage and inflammation require TLR2. Using TLR2(-/-) mice, we demonstrate that TLR2 is required for IR-induced mucosal damage, as well as complement activation and proinflammatory cytokine production. In response to IR, TLR2(-/-) mice have increased serum β2-GPI compared with wild-type mice, but β2-GPI is not deposited on ischemic intestinal tissue. In addition, TLR2(-/-) mice also did not express other novel Ags, suggesting a sequential response. Unlike other TLRs, TLR2(-/-) mice lacked the appropriate Ab repertoire to induce intestinal IR tissue damage or inflammation. Together, these data suggest that, in addition to the inflammatory response, IR-induced injury requires TLR2 for naturally occurring Ab production.
authors.affiliation: Division of Biology, Kansas State University, Manhattan, KS 66506.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Pope
authors.affiliation: Division of Biology, Kansas State University, Manhattan, KS 66506 sdflemin@ksu.edu.
authors.forename: Sherry D
authors.initials: SD
authors.lastname: Fleming
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D015777:Eicosanoids / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D007422:Intestines / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D015427:Reperfusion Injury / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D053482:beta 2-Glycoprotein I / Q000276:immunology / Q000378:metabolism
chemical_list: D000906:Antibodies; D016207:Cytokines; D015777:Eicosanoids; D007075:Immunoglobulin M; D051195:Toll-Like Receptor 2; D053482:beta 2-Glycoprotein I; D003165:Complement System Proteins