In:
Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 117, No. 23 ( 2008-06-10), p. 2977-2985
Abstract:
Background— Group X secretory phospholipase A 2 (sPLA 2 -X) has the most potent hydrolyzing activity toward phosphatidylcholine and elicits a marked release of arachidonic acid among several types of sPLA 2 . sPLA 2 -X is expressed in neutrophils, but its pathogenic role remains unclear. Methods and Results— We generated mice that lack sPLA 2 -X and studied their response to myocardial ischemia/reperfusion. The sPLA 2 -X −/− mice had a significant reduction in myocardial infarct size and a decrease in myocardial myeloperoxidase activity compared with sPLA 2 -X +/+ mice. Myocardial infarct size was also significantly reduced in lethally irradiated sPLA 2 -X +/+ mice reconstituted with sPLA 2 -X −/− bone marrow compared with sPLA 2 -X +/+ bone marrow. The extent of myocardial ischemia/reperfusion injury was comparable between sPLA 2 -X −/− and sPLA 2 -X +/+ mice in Langendorff experiments using isolated hearts and blood-free perfusion buffer, supporting a potential role of sPLA 2 -X in blood in myocardial ischemia/reperfusion injury. In the infarcted myocardium of sPLA 2 -X +/+ mice, sPLA 2 -X was released from neutrophils but not myocardial tissues and platelets and was undetectable in the peripheral serum. The sPLA 2 -X −/− mice had lower accumulation of neutrophils in ischemic myocardium, and the isolated sPLA 2 -X −/− neutrophils had lower release of arachidonic acid and attenuated cytotoxic activities including respiratory burst compared with sPLA 2 -X +/+ neutrophils. The attenuated functions of sPLA 2 -X −/− neutrophils were reversible by the exogenous addition of sPLA 2 -X protein. Furthermore, administration of a sPLA 2 inhibitor reduced myocardial infarct size and suppressed the cytotoxic activity of sPLA 2 -X +/+ neutrophils. Conclusions— Myocardial ischemia/reperfusion injury was attenuated in sPLA 2 -X −/− mice partly through the suppression of neutrophil cytotoxic activities.
Type of Medium:
Online Resource
ISSN:
0009-7322
,
1524-4539
DOI:
10.1161/CIRCULATIONAHA.107.743997
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2008
detail.hit.zdb_id:
1466401-X
detail.hit.zdb_id:
80099-5
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