Cytosolic phospholipase A2 is essential for both the immediate and the delayed phases of eicosanoid generation in mouse bone marrow-derived mast cells
We have used mice in which the gene for cytosolic phospholipase A 2 (cPLA 2 ) has been disrupted to demonstrate the absolute requirement for cPLA 2 in both the immediate and the delayed phases of eicosanoid generation by bone marrow-derived mast cells. For the immediate phase, quantitative analysis...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1999-04, Vol.96 (9), p.4803-4807 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Fujishima, H Sanchez Mejia, R O Bingham, 3rd, C O Lam, B K Sapirstein, A Bonventre, J V Austen, K F Arm, J P |
| description | We have used mice in which the gene for cytosolic phospholipase A 2 (cPLA 2 ) has been disrupted to demonstrate the absolute requirement for cPLA 2 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 cPLA 2 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) D 2 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 β-hexosaminidase. Whereas cPLA 2 is essential for immediate eicosanoid generation by providing arachidonic acid, its role in delayed-phase PGD 2 generation is more complex and involves the activation-dependent induction of prostaglandin endoperoxide synthase 2 and the supply of arachidonic acid for metabolism to PGD 2 . |
| doi_str_mv | 10.1073/pnas.96.9.4803 |
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For the immediate phase, quantitative analysis of the products of the 5-lipoxygenase pathway showed that gene disruption of cPLA 2 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) D 2 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 β-hexosaminidase. Whereas cPLA 2 is essential for immediate eicosanoid generation by providing arachidonic acid, its role in delayed-phase PGD 2 generation is more complex and involves the activation-dependent induction of prostaglandin endoperoxide synthase 2 and the supply of arachidonic acid for metabolism to PGD 2 .</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.96.9.4803</identifier><identifier>PMID: 10220374</identifier><language>eng</language><publisher>United States: National Acad Sciences</publisher><subject>Animals ; Arachidonate 5-Lipoxygenase - metabolism ; Biochemistry ; Biological Sciences ; Bone marrow ; Bone Marrow Cells - metabolism ; Cells ; Cells, Cultured ; Cytosol - metabolism ; Eicosanoids - biosynthesis ; Gene Expression Regulation ; Mast Cells - metabolism ; Mice ; Mice, Knockout ; Phospholipases A - genetics ; Phospholipases A - metabolism ; Phospholipases A2 ; Rodents</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1999-04, Vol.96 (9), p.4803-4807</ispartof><rights>Copyright National Academy of Sciences Apr 27, 1999</rights><rights>Copyright © 1999, The National Academy of Sciences 1999</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/96/9.cover.gif</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC21772/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC21772/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10220374$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fujishima, H</creatorcontrib><creatorcontrib>Sanchez Mejia, R O</creatorcontrib><creatorcontrib>Bingham, 3rd, C O</creatorcontrib><creatorcontrib>Lam, B K</creatorcontrib><creatorcontrib>Sapirstein, A</creatorcontrib><creatorcontrib>Bonventre, J V</creatorcontrib><creatorcontrib>Austen, K F</creatorcontrib><creatorcontrib>Arm, J P</creatorcontrib><title>Cytosolic phospholipase A2 is essential for both the immediate and the delayed phases of eicosanoid generation in mouse bone marrow-derived mast cells</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>We have used mice in which the gene for cytosolic phospholipase A 2 (cPLA 2 ) has been disrupted to demonstrate the absolute requirement for cPLA 2 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 cPLA 2 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) D 2 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 β-hexosaminidase. 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Sanchez Mejia, R O ; Bingham, 3rd, C O ; Lam, B K ; Sapirstein, A ; Bonventre, J V ; Austen, K F ; Arm, J P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p255t-4b87c9aea14a9d9871abed3611134f0eec669b720963e8657bab418438923fc83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Animals</topic><topic>Arachidonate 5-Lipoxygenase - metabolism</topic><topic>Biochemistry</topic><topic>Biological Sciences</topic><topic>Bone marrow</topic><topic>Bone Marrow Cells - metabolism</topic><topic>Cells</topic><topic>Cells, Cultured</topic><topic>Cytosol - metabolism</topic><topic>Eicosanoids - biosynthesis</topic><topic>Gene Expression Regulation</topic><topic>Mast Cells - metabolism</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Phospholipases A - genetics</topic><topic>Phospholipases A - metabolism</topic><topic>Phospholipases A2</topic><topic>Rodents</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fujishima, H</creatorcontrib><creatorcontrib>Sanchez Mejia, R O</creatorcontrib><creatorcontrib>Bingham, 3rd, C O</creatorcontrib><creatorcontrib>Lam, B K</creatorcontrib><creatorcontrib>Sapirstein, A</creatorcontrib><creatorcontrib>Bonventre, J V</creatorcontrib><creatorcontrib>Austen, K F</creatorcontrib><creatorcontrib>Arm, J P</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fujishima, H</au><au>Sanchez Mejia, R O</au><au>Bingham, 3rd, C O</au><au>Lam, B K</au><au>Sapirstein, A</au><au>Bonventre, J V</au><au>Austen, K F</au><au>Arm, J P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cytosolic phospholipase A2 is essential for both the immediate and the delayed phases of eicosanoid generation in mouse bone marrow-derived mast cells</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>1999-04-27</date><risdate>1999</risdate><volume>96</volume><issue>9</issue><spage>4803</spage><epage>4807</epage><pages>4803-4807</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>We have used mice in which the gene for cytosolic phospholipase A 2 (cPLA 2 ) has been disrupted to demonstrate the absolute requirement for cPLA 2 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 cPLA 2 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) D 2 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 β-hexosaminidase. 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| source | Jstor Complete Legacy; MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Animals Arachidonate 5-Lipoxygenase - metabolism Biochemistry Biological Sciences Bone marrow Bone Marrow Cells - metabolism Cells Cells, Cultured Cytosol - metabolism Eicosanoids - biosynthesis Gene Expression Regulation Mast Cells - metabolism Mice Mice, Knockout Phospholipases A - genetics Phospholipases A - metabolism Phospholipases A2 Rodents |
| title | Cytosolic phospholipase A2 is essential for both the immediate and the delayed phases of eicosanoid generation in mouse bone marrow-derived mast cells |
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