title: Reduction in myocardial ischemia/reperfusion injury in group X secretory phospholipase A2-deficient mice.
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.
  
  
  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.
authors.affiliation: Department of Internal Medicine II, Center for Life Science Research, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Fujioka
authors.forename: Yukio
authors.initials: Y
authors.lastname: Saito
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Yano
authors.forename: Hideo
authors.initials: H
authors.lastname: Tezuka
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Ishimoto
authors.forename: Noriko
authors.initials: N
authors.lastname: Suzuki
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Yokota
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Nakamura
authors.forename: Jyun-ei
authors.initials: JE
authors.lastname: Obata
authors.forename: Masaki
authors.initials: M
authors.lastname: Kanazawa
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Kawabata
authors.forename: Kohji
authors.initials: K
authors.lastname: Hanasaki
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Kugiyama
mesh_terms: D000085:Acetates; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000502:physiology; D004452:Echocardiography; D004791:Enzyme Inhibitors / Q000494:pharmacology; D054509:Group X Phospholipases A2 / Q000037:antagonists & inhibitors / Q000097:blood* / Q000235:genetics*; D007211:Indoles; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000276:immunology / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000000981:diagnostic imaging / Q000276:immunology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D009504:Neutrophils / Q000166:cytology / Q000201:enzymology; D009195:Peroxidase / Q000378:metabolism; D011355:Prodrugs / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000085:Acetates; D004791:Enzyme Inhibitors; D007211:Indoles; C428265:LY 329722; D011355:Prodrugs; D017382:Reactive Oxygen Species; D016718:Arachidonic Acid; D009195:Peroxidase; D054509:Group X Phospholipases A2; C516366:Pla2g10 protein, mouse