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Circulating CXC-chemokine concentrations in a murine intestinal ischemia-reperfusion model
Authors:Maheshwari Akhil  Christensen Robert D  Calhoun Darlene A  Dimmitt Reed A  Lacson Atilano
Affiliation:Department of Pediatrics, University of South Florida College of Medicine, Florida, USA. Akhil@peds.uab.edu
Abstract:
BACKGROUND: CXC-chemokines bearing the glutamic acid-leucine-arginine (ELR) motif (ELR+ CXC chemokines) are potent neutrophil chemoattractants and hence may play a role in mucosal injury seen with intestinal ischemia-reperfusion (I/R). METHODS: Serum concentrations of ELR+ CXC chemokines (keratinocyte-derived chemokine(KC) / CXC ligand (CXCL) 1, macrophage inflammatory protein (MIP)-2/CXCL 2/3, lipopolysaccharide-induced CXC chemokine (LIX) / CXCL5, and lungkine/CXCL15) were measured in a murine intestinal I/R model. Fifteen 4-week-old wild-type mice were studied in three subgroups: sham, ischemia (superior mesenteric artery [SMA] clamping for 60 min) and ischemia-reperfusion (SMA clamping for 60 min followed by reperfusion for 90 min). RESULTS: Concentrations of KC/CXCL1 and MIP-2/CXCL2/3 in sham-treated animals (145 +/- 123 and 107 +/- 55 pg/mL, respectively) and the ischemia subgroup (646 +/- 413 and 226 +/- 129 pg/mL) were similar, but concentrations were signifcantly higher with reperfusion (6398 +/- 2297, p < .001 and 874 +/- 790 pg/mL, p = .04). LIX/CXCL5 and lungkine/CXCL15 concentrations did not change significantly with ischemia or following I/R. KC/CXCL1 and MIP-2/CXCL2/3 concentrations correlated positively with the severity of mucosal injury and with each other, whereas a negative relationship was observed between LIX/CXCL5 concentrations and microscopic injury scores. CONCLUSIONS: Development of mucosal injury in intestinal I/R is associated with increased serum concentrations of KC/CXCL1 and MIP-2/CXCL2/3, but not with those of LIX/CXCL5 and lungkine/CXCL15.
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