Neutrophil protein kinase Cδ as a mediator of stroke-reperfusion injury
Neutrophil protein kinase Cδ as a mediator of stroke-reperfusion injury
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DOI：
10.1172/jc1200421655
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发表时间：
2004-07-01
影响因子：
15.9
通讯作者：
Messing, RO
中科院分区：
文献类型：
--
作者：
Chou, WH;Choi, DS;Messing, RO
溶栓治疗被广泛应用于急性缺血性卒中的干预，但循环重建却可能引发再灌注损伤。在这里，我们描述了对缺乏蛋白激酶C增量(PKCDelta)的小鼠的研究，表明该酶的缺失显著减少了短暂性缺血后的再灌注损伤。这与外周血中性粒细胞向梗塞组织的渗透减少以及体外中性粒细胞黏附、迁移、呼吸爆发和脱颗粒受损有关。全身照射后，来自PKC Delta缺失小鼠的骨髓移植减少了WT小鼠的脑梗塞范围并改善了神经预后，而来自WT捐赠者的骨髓移植增加了PKC Delta缺失小鼠的脑梗塞并恶化了神经学评分。这些结果表明中性粒细胞PKC Delta在再灌注损伤中起重要作用，并有力地提示PKC Delta抑制剂在卒中的治疗中可能是有用的。
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.