A novel inhibitor of the alternative pathway of complement attenuates intestinal ischemia/reperfusion-induced injury.
Complement activation has been demonstrated to contribute significantly to the expression of IR-induced tissue damage. Each of the three complement pathways, classic, alternative, and lectin, has been implicated in the instigation of tissue pathology. In this study, we used a selective inhibitor of the alternative pathway, that is, a soluble form of complement receptor of the immunoglobulin superfamily (CRIg-Fc) to determine whether it can prevent IR tissue injury. We demonstrate that treatment of C57B1/6 mice prior to mesenteric IR prevents local (intestinal) and remote (lung) injury by limiting deposition of complement and entry of polymorphonuclear cells to the sites of injury. Our results show that CRIg-Fc represents a candidate to limit IR injury as it occurs in various clinical conditions.
Chen
Jie
J
Division of Rheumatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
Crispín
José C
JC
Dalle Lucca
Jurandir
J
Tsokos
George C
GC
D055371:Acute Lung Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D000818:Animals; D001402:B-Lymphocytes / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D003170:Complement Pathway, Alternative / Q000187:drug effects / Q000502:physiology*; D007141:Immunoglobulin Fc Fragments / Q000494:pharmacology / Q000627:therapeutic use*; D007421:Intestine, Small / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology*; D008643:Mesentery / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D020556:Neutrophil Infiltration / Q000187:drug effects; D011951:Receptors, Complement / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D013601:T-Lymphocytes / Q000473:pathology
D007141:Immunoglobulin Fc Fragments; D011951:Receptors, Complement; D011993:Recombinant Fusion Proteins; C509992:VSIG4 protein, mouse