Hypexia/reoxygenation causes inflammatory response in transgenic sickle mice but not in normal mice

D. K. Kaul, R. P. Hebbel

Research output: Contribution to journalArticlepeer-review

307 Scopus citations

Abstract

In sickle cell anemia, the initiation, progression, and resolution of a vasoocclusive episode may present features of ischemia-reperfusion injury, with recurrent episodes of ischemia/hypoxia and reoxygenation promoting inflammation. Here, we have tested the hypothesis that hypoxia/reoxygenation triggers inflammation in the transgenic sickle mouse. In these mice, even at ambient air, peripheral leukocyte counts are elevated by 1.7-fold and neutrophil counts by almost 3-fold. Two hours of hypoxia, followed by reoxygenation, induced a greater than normal rolling flux and adhesion of leukocytes in these mice, but no leukocyte extravasation. When 3 hours of hypoxia was followed by reoxygenation, sickle mice, but not normal mice, showed a distinct inflammatory response characterized by an increased number of adherent and emigrated leukocytes. Because these events, which are exaggerated in sickle mice, are not seen in response to hypoxia alone, we conclude that they represent a form of reperfusion injury. Studies using an H2O2-sensitive probe revealed clear evidence of oxidant production in vascular endothelial cells after hypoxia/reoxygenation in sickle mice. Infusion of an anti-P-selectin antibody, but not an anti-E-selectin antibody, completely inhibited this inflammatory response and significantly increased wall shear rates. These findings suggest that leukocyte-endothelium interaction contribute to vasoocclusive events in the sickle mice and perhaps in human sickle disease.

Original languageEnglish (US)
Pages (from-to)411-420
Number of pages10
JournalJournal of Clinical Investigation
Volume106
Issue number3
DOIs
StatePublished - 2000

Fingerprint Dive into the research topics of 'Hypexia/reoxygenation causes inflammatory response in transgenic sickle mice but not in normal mice'. Together they form a unique fingerprint.

Cite this