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PMID: 10220374 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Cytosolic phospholipase A2 is essential for both the immediate and the delayed phases of eicosanoid generation in mouse bone marrow-derived mast cells.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 96 ·No. 9 ·1999-04-27 ·Pages 4803-7

Fujishima H, Sanchez Mejia RO, Bingham CO, Lam BK, Sapirstein A, Bonventre JV, Austen KF, Arm JP

Abstract

We have used mice in which the gene for cytosolic phospholipase A2 (cPLA2) has been disrupted to demonstrate the absolute requirement for cPLA2 in both the immediate and the delayed phases of eicosanoid generation by bone marrow-derived mast cells. For the immediate phase, quantitative analysis of the products of the 5-lipoxygenase pathway showed that gene disruption of cPLA2 prevented the provision of arachidonic acid substrate for biosynthesis of proximal intermediates. By analogy, we conclude that arachidonic acid substrate was also not available to prostaglandin endoperoxide synthase 1 in the immediate phase of prostaglandin (PG) D2 generation. These defects occurred with two distinct stimuli, stem cell factor and IgE/antigen, which were, however, sufficient for signal transduction defined by exocytosis of beta-hexosaminidase. Whereas cPLA2 is essential for immediate eicosanoid generation by providing arachidonic acid, its role in delayed-phase PGD2 generation is more complex and involves the activation-dependent induction of prostaglandin endoperoxide synthase 2 and the supply of arachidonic acid for metabolism to PGD2.

MeSH Terms
Animals Arachidonate 5-Lipoxygenase/metabolism Bone Marrow Cells/metabolism Cells, Cultured Cytosol/metabolism Eicosanoids/biosynthesis Gene Expression Regulation Mast Cells/metabolism Mice Mice, Knockout Phospholipases A/genetics,metabolism Phospholipases A2
Chemicals
Eicosanoids Arachidonate 5-Lipoxygenase Phospholipases A Phospholipases A2
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Fujishima H
Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
Sanchez Mejia R O
Bingham C O
Lam B K
Sapirstein A
Bonventre J V
Austen K F
Arm J P
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.96.9.4803
Published
1999-04-27
Pages
4803-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC21772
Subset
IM
Grants
NINDS NIH HHS · P01 NS010828 · United States
NHLBI NIH HHS · P01 HL036110 · United States
NIAID NIH HHS · U19 AI031599 · United States
NIAID NIH HHS · AI31599 · United States
NIDDK NIH HHS · R37 DK039773 · United States
NIAID NIH HHS · AI22531 · United States
NHLBI NIH HHS · HL36110 · United States
NINDS NIH HHS · P50 NS010828 · United States
NINDS NIH HHS · F32 NS010828 · United States
NIDDK NIH HHS · P01 DK038452 · United States
NIDDK NIH HHS · R01 DK039773 · United States
HSRD VA · TPP 97-001 · United States
NIAID NIH HHS · P01 AI031599 · United States
External Links
PubMed source DOI: 10.1073/pnas.96.9.4803 PMC Full Text View journal details
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