Lipocortin 1 Protects Against Splanchnic Artery Occlusion and Reperfusion Injury by Affecting Neutrophil Migration

Salvatore Cuzzocrea, Anitaben Tailor, Basilia Zingarelli, Andrew L. Salzman, Roderick J. Flower, Csaba Szabo, Mauro Perretti

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Abstract

Splanchnic artery occlusion and reperfusion (SAO/R) shock was induced in rats by clamping both the superior mesenteric artery and the celiac trunk for 45 min, followed by release of the clamp (60-min reperfusion). Following this reperfusion period, rats developed a fall in mean arterial blood pressure, associated with a significant increase in tissue myeloperoxidase (MPO) activity in the intestine and a marked histologic injury to the distal ileum. Treatment of rats with a lipocortin-1 (LC1)-derived N-terminal peptide, peptide Ac2-26, dose-dependently (0.125-0.5 mg/kg s.c.) reduced the progressive fall in blood pressure and prevented the infiltration of neutrophils into the reperfused intestine (reduced MPO activity). The LC1 peptide also reduced the degree of ischemia/reperfusion injury in the bowel as evaluated by histologic examination. The glucocorticoid dexamethasone (0.1 mg/kg s.c., -1 h) also produced a marked improvement in SAO/R shock (i.e., maintained mean arterial blood pressure and reduced tissue MPO activity), and this was reversed by pretreatment with two different antisera raised against the LC1 pharmacophore. Peptide Ac2-26 (0.5 mg/kg s.c., -30 min) reduced (>60%) the extent of IL-1β-induced cell emigration and significantly attenuated (∼45%) the number of adherent leukocytes in the rat mesenteric vascular bed, as assessed by video microscopy. These results suggest that LC1 inhibits neutrophil migration and accumulation into reperfused tissues, thereby ameliorating the outcome of SAO/R shock.

Original languageEnglish (US)
Pages (from-to)5089-5097
Number of pages9
JournalJournal of Immunology
Volume159
Issue number10
StatePublished - Nov 15 1997
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

Cite this

Cuzzocrea, S., Tailor, A., Zingarelli, B., Salzman, A. L., Flower, R. J., Szabo, C., & Perretti, M. (1997). Lipocortin 1 Protects Against Splanchnic Artery Occlusion and Reperfusion Injury by Affecting Neutrophil Migration. Journal of Immunology, 159(10), 5089-5097.