Neutrophil protein kinase Cδ as a mediator of stroke-reperfusion injury

Wen Hai Chou, Doo Sup Choi, Hong Zhang, Dezhi Mu, Tom McMahon, Viktor N. Kharazia, Clifford A. Lowell, Donna M. Ferriero, Robert O. Messing

Research output: Contribution to journalArticle

106 Scopus citations

Abstract

Thrombolysis is widely used to intervene in acute ischemic stroke, but reestablishment of circulation may paradoxically initiate a reperfusion injury. Here we describe studies with mice lacking protein kinase Cδ (PKCδ) showing that absence of this enzyme markedly reduces reperfusion injury following transient ischemia. This was associated with reduced infiltration of peripheral blood neutrophils into infarcted tissue and with impaired neutrophil adhesion, migration, respiratory burst, and degranulation in vitro. Total body irradiation followed by transplantation with bone marrow from PKCδ-null mice donors reduced infarct size and improved neurological outcome in WT mice, whereas marrow transplantation from WT donors increased infarction and worsened neurological scores in PKCδ-null mice. These results indicate an important role for neutrophil PKCδ in reperfusion injury and strongly suggest that PKCδ inhibitors could prove useful in the treatment of stroke.

Original languageEnglish (US)
Pages (from-to)49-56
Number of pages8
JournalJournal of Clinical Investigation
Volume114
Issue number1
DOIs
StatePublished - Jul 2004

ASJC Scopus subject areas

  • Medicine(all)

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    Chou, W. H., Choi, D. S., Zhang, H., Mu, D., McMahon, T., Kharazia, V. N., Lowell, C. A., Ferriero, D. M., & Messing, R. O. (2004). Neutrophil protein kinase Cδ as a mediator of stroke-reperfusion injury. Journal of Clinical Investigation, 114(1), 49-56. https://doi.org/10.1172/JCI200421655