Role of group V phospholipase A2 in zymosan-induced eicosanoid generation and vascular permeability revealed by targeted gene disruption.
Conclusions regarding the contribution of low molecular weight secretory phospholipase A2 (sPLA2) enzymes in eicosanoid generation have relied on data obtained from transfected cells or the use of inhibitors that fail to discriminate between individual members of the large family of mammalian sPLA2 enzymes. To elucidate the role of group V sPLA2, we used targeted gene disruption to generate mice lacking this enzyme. Zymosan-induced generation of leukotriene C4 and prostaglandin E2 was attenuated approximately 50% in peritoneal macrophages from group V sPLA2-null mice compared with macrophages from wild-type littermates. Furthermore, the early phase of plasma exudation in response to intraperitoneal injection of zymosan and the accompanying in vivo generation of cysteinyl leukotrienes were markedly attenuated in group V sPLA2-null mice compared with wild-type controls. These data provide clear evidence of a role for group V sPLA2 in regulating eicosanoid generation in response to an acute innate stimulus of the immune response both in vitro and in vivo, suggesting a role for this enzyme in innate immunity.
Satake
Yoshiyuki
Y
Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
Diaz
Bruno L
BL
Balestrieri
Barbara
B
Lam
Bing K
BK
Kanaoka
Yoshihide
Y
Grusby
Michael J
MJ
Arm
Jonathan P
JP
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology*; D015777:Eicosanoids / Q000378:metabolism*; D017353:Gene Deletion; D054505:Group V Phospholipases A2; D007109:Immunity / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D010741:Phospholipases A / Q000235:genetics / Q000378:metabolism*; D054467:Phospholipases A2; D015054:Zymosan / Q000378:metabolism / Q000494:pharmacology
D015777:Eicosanoids; D015054:Zymosan; D010741:Phospholipases A; D054505:Group V Phospholipases A2; D054467:Phospholipases A2; C101424:phospholipase A2-V, Trimeresurus