title: C5a inhibitor protects against ischemia/reperfusion injury in rat small intestine.
abstract: 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.
authors.affiliation: Institute of Surgical Research, Faculty of Medicine, University of Szeged, 6 Szőkefalvi-Nagy Béla Street, Szeged, 6720, Hungary.
authors.forename: Eszter
authors.initials: E
authors.lastname: Tuboly
authors.affiliation: Department of Molecular Toxicology.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Futakuchi
authors.affiliation: Institute of Surgical Research, Faculty of Medicine, University of Szeged, 6 Szőkefalvi-Nagy Béla Street, Szeged, 6720, Hungary.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Varga
authors.affiliation: Institute of Surgical Research, Faculty of Medicine, University of Szeged, 6 Szőkefalvi-Nagy Béla Street, Szeged, 6720, Hungary.
authors.forename: Daniel
authors.initials: D
authors.lastname: Érces
authors.affiliation: Institute of Surgical Research, Faculty of Medicine, University of Szeged, 6 Szőkefalvi-Nagy Béla Street, Szeged, 6720, Hungary.
authors.forename: Tünde
authors.initials: T
authors.lastname: Tőkés
authors.affiliation: Institute of Surgical Research, Faculty of Medicine, University of Szeged, 6 Szőkefalvi-Nagy Béla Street, Szeged, 6720, Hungary.
authors.forename: Andras
authors.initials: A
authors.lastname: Mészáros
authors.affiliation: Institute of Surgical Research, Faculty of Medicine, University of Szeged, 6 Szőkefalvi-Nagy Béla Street, Szeged, 6720, Hungary.
authors.forename: József
authors.initials: J
authors.lastname: Kaszaki
authors.affiliation: Department of Molecular Toxicology.
authors.forename: Masumi
authors.initials: M
authors.lastname: Suzui
authors.affiliation: Department of Immunology, Graduate School of Medical Sciences, Nagoya City University, 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, 467-8601.
authors.forename: Masaki
authors.initials: M
authors.lastname: Imai
authors.affiliation: Research Institute for Protein Science, 2-18 Nakayama-cho, Mizuho-ku, Nagoya, 467-0803, Japan.
authors.forename: Alan
authors.initials: A
authors.lastname: Okada
authors.affiliation: Professor Emeritus, Nagoya City University.
authors.forename: Noriko
authors.initials: N
authors.lastname: Okada
authors.affiliation: Institute of Surgical Research, Faculty of Medicine, University of Szeged, 6 Szőkefalvi-Nagy Béla Street, Szeged, 6720, Hungary.
authors.forename: Mihály
authors.initials: M
authors.lastname: Boros
authors.affiliation: Professor Emeritus, Nagoya City University.
authors.forename: Hidechika
authors.initials: H
authors.lastname: Okada
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D049109:Cell Proliferation; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000276:immunology; D007150:Immunohistochemistry; D007410:Intestinal Diseases / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000473:pathology; D007421:Intestine, Small / Q000098:blood supply* / Q000473:pathology; D008297:Male; D009504:Neutrophils; D051381:Rats; D017207:Rats, Sprague-Dawley; D044087:Receptor, Anaphylatoxin C5a / Q000037:antagonists & inhibitors* / Q000276:immunology; D015427:Reperfusion Injury / Q000517:prevention & control*; D012697:Serine Endopeptidases / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D044087:Receptor, Anaphylatoxin C5a; D012697:Serine Endopeptidases; D014409:Tumor Necrosis Factor-alpha; C496868:C5ar2 protein, rat; C539355:CD68 protein, rat; D000097382:CD68 Molecule; C497444:Hif1a protein, rat; C041833:complement C5a-inhibitors
keywords: complement C5a; hypoxia-induced factor 1-alpha; ischemia; macrophage