title: Neutrophil protein kinase Cdelta as a mediator of stroke-reperfusion injury.
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 Cdelta (PKCdelta) 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 PKCdelta-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 PKCdelta-null mice. These results indicate an important role for neutrophil PKCdelta in reperfusion injury and strongly suggest that PKCdelta inhibitors could prove useful in the treatment of stroke.
authors.affiliation: Ernest Gallo Clinic and Research Center at the University of California San Francisco, Emeryville, California 94608, USA.
authors.forename: Wen-Hai
authors.initials: WH
authors.lastname: Chou
authors.forename: Doo-Sup
authors.initials: DS
authors.lastname: Choi
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Dezhi
authors.initials: D
authors.lastname: Mu
authors.forename: Tom
authors.initials: T
authors.lastname: McMahon
authors.forename: Viktor N
authors.initials: VN
authors.lastname: Kharazia
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Lowell
authors.forename: Donna M
authors.initials: DM
authors.lastname: Ferriero
authors.forename: Robert O
authors.initials: RO
authors.lastname: Messing
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D005091:Exons; D002546:Ischemic Attack, Transient / Q000097:blood / Q000235:genetics / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000201:enzymology*; D011493:Protein Kinase C / Q000097:blood* / Q000172:deficiency / Q000235:genetics; D051745:Protein Kinase C-delta; D011995:Recombination, Genetic; D015427:Reperfusion Injury / Q000097:blood* / Q000201:enzymology
chemical_list: C497259:Prkcd protein, mouse; D011493:Protein Kinase C; D051745:Protein Kinase C-delta