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Role of group V phospholipase A2 in zymosan-induced eicosanoid generation and vascular permeability revealed by targeted gene disruption
- Source :
- The Journal of biological chemistry. 279(16)
- Publication Year :
- 2004
-
Abstract
- 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.
- Subjects :
- Pharmacology
Biochemistry
Phospholipases A
Article
Group V Phospholipases A2
Capillary Permeability
chemistry.chemical_compound
Mice
Immune system
Phospholipase A2
In vivo
medicine
Animals
Prostaglandin E2
Molecular Biology
Mice, Inbred BALB C
Innate immune system
Leukotriene C4
biology
Zymosan
Immunity
Cell Biology
Molecular biology
Phospholipases A2
chemistry
Eicosanoid
biology.protein
Eicosanoids
Gene Deletion
medicine.drug
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 279
- Issue :
- 16
- Database :
- OpenAIRE
- Journal :
- The Journal of biological chemistry
- Accession number :
- edsair.doi.dedup.....686edb1826d8bea94442942dd3ec07fb