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C5a inhibitor protects against ischemia/reperfusion injury in rat small intestine
Author(s) -
Tuboly Eszter,
Futakuchi Mitsuru,
Varga Gabriella,
Érces Daniel,
Tőkés Tünde,
Mészáros Andras,
Kaszaki József,
Suzui Masumi,
Imai Masaki,
Okada Alan,
Okada Noriko,
Boros Mihály,
Okada Hidechika
Publication year - 2016
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/1348-0421.12338
Subject(s) - ischemia , hypoxia (environmental) , reperfusion injury , biology , superior mesenteric artery , inflammation , inhibitory postsynaptic potential , immunology , pharmacology , mesenteric ischemia , intestinal ischemia , small intestine , pathology , medicine , endocrinology , chemistry , organic chemistry , oxygen
Acute mesenteric ischemia (AMI) is caused by considerable intestinal injury, which is associated with intestinal ischemia followed by reperfusion. To elucidate the mechanisms of ischemia/reperfusion injuries, a C5a inhibitory peptide termed AcPepA was used to examine the role of C5a anaphylatoxin, induction of inflammatory cells, and cell proliferation of the intestinal epithelial cells in an experimental AMI model. In this rat model, the superior mesenteric artery was occluded and subsequently reperfused (Induce‐I/R). Other groups were treated with AcPepA before ischemia or reperfusion. Induce‐I/R induced injuries in the intestine and AcPepA significantly decreased the proportion of severely injured villi. Induce‐I/R induced secondary receptor for C5a‐positive polymorphonuclear leukocytes in the vessels and CD204‐positive macrophages near the injured site; this was correlated with hypoxia‐induced factor 1‐alpha‐positive cells. Induction of these inflammatory cells was attenuated by AcPepA. In addition, AcPepA increased proliferation of epithelial cells in the villi, possibly preventing further damage. Therefore, Induce‐I/R activates C5a followed by the accumulation of polymorphonuclear leukocyte and hypoxia‐induced factor 1‐alpha‐producing macrophages, leading to villus injury. AcPepA, a C5a inhibitory peptide, blocks the deleterious effects of C5a, indicating it has a therapeutic effect on the inflammatory consequences of experimental AMI.