Participation of Cytosolic Phospholipase A2 in Eicosanoid Generation by Mouse Bone Marrow-Derived Mast Cells

  • Bruno L. Diaz
  • Hiroshi Fujishima
  • Adam Sapirstein
  • Joseph V. Bonventre
  • Jonathan P. Arm
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 507)


Leukotrienes and prostaglandins, derived from the oxidative metabolism of arachidonic acid12are potent lipid mediators of tissue inflammation.34The first step in the generation of these eicosanoids, is the liberation of esterified arachidonic acid from the sn-2 position of cell membrane glycerophospholipids by the action of phospholipase A2 (PLA2)5. The family of mammalian PLA2enzymes includes the 85-kDa group IV cytosolic PLA2(cPLA2); at least eight low molecular weight, cysteine-rich PLA2enzymes; and calcium-independent species of PLA2.6


Arachidonic Acid Stem Cell Factor Cytosolic Phospholipase Secretory Phospholipase PLA2 Enzyme 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    B. Samuelsson, Leukotrienes: mediators of immediate hypersensitivity reactions and inflammationScience220:568 (1983).PubMedCrossRefGoogle Scholar
  2. 2.
    W.L. Smith, Prostanoid biosynthesis and mechanisms of actionAm. J. Physiol.263:F 181 (1992).Google Scholar
  3. 3.
    W.R. Henderson, The role of leukotrienes in inflammationAnn. Intern. Med. I21:684 (1994).CrossRefGoogle Scholar
  4. 4.
    E.J. Goetz!, S. An and W.L. Smith, Specificity of expression and effects of eicosanoid mediators in normal physiology and human diseasesFASEB J.9:1051 (1995).Google Scholar
  5. 5.
    E.A. Dennis, Diversity of group types, regulation, and function of phospholipase A 2J. Biol. Chem.269:13057 (1994).PubMedGoogle Scholar
  6. 6.
    E.A Dennis, The growing phospholipase A2superfamily of signal transduction enzymesTrends Biochem. Sci.22:1 (1997).PubMedCrossRefGoogle Scholar
  7. 7.
    M. Murakami, R. Matsumoto, K.F. Austen, and J.P. Arm, Prostaglandin endoperoxide synthase-1 and -2 couple to different transmembrane stimuli to generate prostaglandin D2 in mouse bone marrow-derived mast cells, J.Biol. Chem.269:22269 (1994).PubMedGoogle Scholar
  8. 8.
    M. Murakami, C.O. Bingham III, R. Matsumoto, K.F. Austen, and J.P. Arm, IgE-dependent activation of cytokine-primed mouse cultured mast cells induces a delayed phase of prostaglandin D2 generation via prostaglandin endoperoxide synthase-2J. Immunol.155:4445 (1995).PubMedGoogle Scholar
  9. 9.
    S.T. Reddy and H.R. Herschman, Prostaglandin synthase-1 and prostaglandin synthase-2 are coupled to distinct phospholipases for the generation of prostaglandin D2 in activated mast cellsJ. Biol. Chem.272:3231 (1997).PubMedCrossRefGoogle Scholar
  10. 10.
    R. Kawata, S.T. Reddy, B. Wolner and H.R. Herschman, Prostaglandin synthase 1 and prostaglandin synthase 2 both participate in activation-induced prostaglandin D2 production in mast cellsJ. Immunol.155:818 (1995).PubMedGoogle Scholar
  11. 11.
    M. Murakami, K.F. Austen, and J.P. Arm, The immediate phase of c-kit ligand stimulation of mouse bone marrow-derived mast cells elicits rapid leukotriene C4 generation through posttranslational activation of cytosolic phospholipase A2and 5-lipoxygenaseJ. Exp. Med.I82:197 (1995).CrossRefGoogle Scholar
  12. 12.
    J.V. Bonventre, Z. Huang, M.R. Taheri, E. O’Leary, E. Li, M.A. Moskowitz and A. Sapirstein, Reduced fertility and postischaemic brain injury in mice deficient in cytosolic phospholipase A2Nature390:622 (1997).PubMedCrossRefGoogle Scholar
  13. 13.
    H. Fujishima, R.O. Sanchez Mejia, C.O. Bingham III, B.K. Lam, A. Sapirstein, J.V. Bonventre, K.F. Austen and J.P. Arm, Cytosolic phospholipase A2 is essential for both the immediate and the delayed phases of eicosanoid generation in mouse bone marrow-derived mast cellsProc Nat! Acad Sci U S A.96:4803 (1999).CrossRefGoogle Scholar
  14. 14.
    S.T. Reddy, M.V. Winstead, J.A. Tischfield and H.R. Herschman, Analysis of the secretory phospholipase A2 that mediates prostaglandin production in mast cellsJ. Biol. Chem.272:13591 (1997).PubMedCrossRefGoogle Scholar
  15. 15.
    M. Murakami, S. Shimbara, T. Kambe, H. Kuwata, M.V. Winstead, J.A. Tischfield and I. Kudo, The functions of five distinct mammalian phospholipase A2S in regulating arachidonic acid release. Type IIa and type V secretory phospholipase A2S are functionally redundant and act in concert with cytosolic phospholipase A2J. Biol. Chem.273:14411 (1998).PubMedCrossRefGoogle Scholar
  16. 16.
    J. Balsinde and E.A. Dennis, Distinct roles in signal transduction for each of the phospholipase A2 enzymes present in P388D, macrophagesJ. Biol. Chem.271: 6758 (1996).PubMedCrossRefGoogle Scholar
  17. 17.
    L.A.Marshall, B. Bolognese, J.D. Winkler and A. Roshak, Depletion of human monocyte 85-kDa phospholipase A2 does not alter leukotriene formationJ. Biol. Chem.272:759 (1997).PubMedCrossRefGoogle Scholar
  18. 18.
    A. Rossi, P. Kapahi, G. Natoli, T. Takahashi, Y. Chen, M. Karin and M.G. Santoro, Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IkappaB kinaseNature.403:103 (2000).PubMedCrossRefGoogle Scholar
  19. 19.
    E.A. Meade, T.M. McIntyre, G.A. Zimmerman and S.M. Prescott, Peroxisome proliferators enhance cyclooxygenase-2 expression in epithelial cellsJ Biol Chem.274:8328 (1999).PubMedCrossRefGoogle Scholar
  20. 20.
    C.O. Bingham III, M. Murakami, H. Fujishima, J.E. Hunt, K.F. Austen and J.P. Arm, A heparin-sensitive phospholipase A2 and prostaglandin endoperoxide synthase-2 are functionally linked in the delayed phase of prostaglandin D2 generation in mouse bone marrow-derived mast cellsJ. Biol. Chem.271:25936 (1996).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Bruno L. Diaz
    • 1
    • 3
  • Hiroshi Fujishima
    • 1
    • 3
  • Adam Sapirstein
    • 2
    • 6
  • Joseph V. Bonventre
    • 1
    • 5
    • 7
  • Jonathan P. Arm
    • 1
    • 3
    • 4
  1. 1.Department of MedicineHarvard Medical SchoolBoston
  2. 2.Department of Anesthesia and Critical CareHarvard Medical SchoolBoston
  3. 3.Division of Rheumatology, Immunology, and AllergyBrigham and Women’s HospitalBoston
  4. 4.Partners’ Asthma CenterBrigham and Women’s HospitalBoston
  5. 5.Medical ServicesMassachusetts General HospitalBoston
  6. 6.Anesthesia ServicesMassachusetts General HospitalBoston
  7. 7.Division of Health SciencesHarvard-Massachusetts Institute of TechnologyBoston

Personalised recommendations