C5a inhibitor protects against ischemia/reperfusion injury in rat small intestine |
| |
Authors: | Eszter Tuboly Mitsuru Futakuchi Gabriella Varga Daniel Érces Tünde Tőkés Andras Mészáros József Kaszaki Masumi Suzui Masaki Imai Alan Okada Noriko Okada Mihály Boros Hidechika Okada |
| |
Affiliation: | 1. Institute of Surgical Research, Faculty of Medicine, University of Szeged, Szeged, 6720, Hungary;2. Department of Molecular Toxicology;3. Department of Immunology, Graduate School of Medical Sciences, Nagoya City University, Mizuho‐ku, Nagoya, 467‐8601;4. Research Institute for Protein Science, Mizuho‐ku, Nagoya, 467‐0803, Japan;5. Professor EmeritusNagoya City University |
| |
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. |
| |
Keywords: | complement C5a hypoxia‐induced factor 1‐alpha ischemia macrophage |
|
|