Dataset Information

Peptide binding to cleaved CD31 dampens ischemia/reperfusion-induced intestinal injury.

ABSTRACT: CD31 is a key transmembrane neutrophil immunoregulatory receptor. Mesenteric ischemia/reperfusion-induced neutrophil activation leads to a massive cleavage and shedding of the most extracellular domains of CD31 into plasma, enhancing the deleterious effect of neutrophil activation. We have evaluated the preventive therapeutic potential of an engineered synthetic octapeptide (P8RI), which restores the inhibitory intracellular signaling of cleaved CD31, in an experimental model of acute mesenteric ischemia/reperfusion.In a randomized, controlled, and experimenter-blinded preclinical study, mesenteric ischemia/reperfusion (I/R) was induced in Wistar rats by superior mesenteric artery occlusion for 30 min followed by 4 h of reperfusion. Three groups of rats were compared: I/R + saline perfusion (I/R controls group, n?=?7), I/R + preventive P8RI perfusion (P8RI group, n?=?7), and sham-operated rats + saline perfusion (sham group, n?=?7).Compared with I/R controls, P8RI perfusion significantly decreased intestinal ischemia/reperfusion injury (Chiu's score, P?=?0.01; epithelial area, P?=?0.001) and bacterial translocation (plasma Escherichia coli DNA, P?=?0.04) and could limit intestinal bleeding (P?=?0.09). P8RI decreased neutrophil activation assessed by matrix metalloproteinase-9 release in plasma (P?

SUBMITTER: Hoang QT

PROVIDER: S-EPMC6093833 | biostudies-other | 2018 Aug

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Peptide binding to cleaved CD31 dampens ischemia/reperfusion-induced intestinal injury.

Hoang Quoc Thang QT Nuzzo Alexandre A Louedec Liliane L Delbosc Sandrine S Andreata Francesco F Khallou-Laschet Jamila J Assadi Maksud M Montravers Philippe P Longrois Dan D Corcos Olivier O Caligiuri Giuseppina G Nicoletti Antonino A Michel Jean-Baptiste JB Tran-Dinh Alexy A

Intensive care medicine experimental 20180815 1

<h4>Background</h4>CD31 is a key transmembrane neutrophil immunoregulatory receptor. Mesenteric ischemia/reperfusion-induced neutrophil activation leads to a massive cleavage and shedding of the most extracellular domains of CD31 into plasma, enhancing the deleterious effect of neutrophil activation. We have evaluated the preventive therapeutic potential of an engineered synthetic octapeptide (P8RI), which restores the inhibitory intracellular signaling of cleaved CD31, in an experimental model ...[more]

PMID: 30112663

Similar Datasets

Project description:Intestinal ischemia-reperfusion (I/R) injury is a devastating complication when the blood supply is reflowed in ischemic organs. Gastrin has critical function in regulating acid secretion, proliferation, and differentiation in the gastric mucosa. We aimed to determine whether gastrin has an effect on intestinal I/R damage. Intestinal I/R injury was induced by 60-min occlusion of the superior mesenteric artery followed by 60-min reperfusion, and the rats were induced to be hypergastrinemic by pretreated with omeprazole or directly injected with gastrin. Some hypergastrinemic rats were injected with cholecystokinin-2 (CCK-2) receptor antagonist prior to I/R operation. After the animal surgery, the intestine was collected for histological analysis. Isolated intestinal epithelial cells or crypts were harvested for RNA and protein analysis. CCK-2 receptor expression, intestinal mucosal damage, cell apoptosis, and apoptotic protein caspase-3 activity were measured. We found that high gastrin in serum significantly reduced intestinal hemorrhage, alleviated extensive epithelial disruption, decreased disintegration of lamina propria, downregulated myeloperoxidase activity, tumor necrosis factor-?, and caspase-3 activity, and lead to low mortality in response to I/R injury. On the contrary, CCK-2 receptor antagonist L365260 could markedly impair intestinal protection by gastrin on intestinal I/R. Severe edema of mucosal villi with severe intestinal crypt injury and numerous intestinal villi disintegrated were observed again in the hypergastrinemic rats with L365260. The survival in the hypergastrinemic rats after intestinal I/R injury was shortened by L365260. Finally, gastrin could remarkably upregulated intestinal CCK-2 receptor expression. Our data suggest that gastrin by omeprazole remarkably attenuated I/R induced intestinal injury by enhancing CCK-2 receptor expression and gastrin could be a potential mitigator for intestinal I/R damage in the clinical setting.

Dataset Information

Peptide binding to cleaved CD31 dampens ischemia/reperfusion-induced intestinal injury.

Publications

Peptide binding to cleaved CD31 dampens ischemia/reperfusion-induced intestinal injury.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets