Volume 70, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


Lipid mediators play important roles in the pathogenesis of malaria. Phospholipase As are enzymes involved in the production of these mediators, and they function in inflammation. Among them, cytosolic phospholipase A (cPLA) is a key enzyme in the metabolism of arachidonic acid, the first intermediate in the production of lipid mediators. ANKA causes cerebral malaria in CL57B/6 mice, and we recently produced cPLA-deficient mice with this background. With the expectation of reduced pathogenicity, we performed experimental infection in these mice. Unexpectedly, the infected mice developed cerebral malaria and died at the same time as the control mice, while the parasitemia progressed similarly in both groups. These observations suggest that secretory PLAs rather than cPLA may be involved in the aggravation, although possible compensation by the induction of other enzymes has not been excluded. The present findings are expected to help clarify the involvement of various phospholipase As in malaria.


Article metrics loading...

Loading full text...

Full text loading...



  1. Clark IA, Hunt NH, 1986. Increased production of arachidonate netabolites by peritoneal cells of mice infected with Plasmodium vinckei vinckei. Aust J Exp Biol Med Sci 64 : 415–418.
  2. Weston MJ, Jackman N, Rudge C, Bowles J, Brady C, Bielawska C, O’Grady J, 1982. Prostacyclin in falciparum malaria (letter). Lancet 2 : 609.
  3. Sliwa K, Grundmann HJ, Neifer S, Chaves MF, Sahlmuller G, Blistein-Willinger E, Bienzle U, Kremsner PG, 1991. Prevention of murine cerebral malaria by a stable prostacyclin analog. Infect Immun 59 : 3846–3848.
  4. Xiao L, Patterson PS, Yang C, Lal AA, 1999. Role of eicosanoids in the pathogenesis of murine cerebral malaria. Am J Trop Med Hyg 60 : 668–673.
  5. Perkins DJ, Kremsner PG, Weinberg JB, 2001. Inverse relationship of plasma prostaglandin E2 and blood mononuclear cell cyclooxygenase-2 with disease severity in children with Plasmodium falciparum malaria. J Infect Dis 183 : 113–118.
  6. Deininger MH, Kremsner PG, Meyermann R, Schluesener HJ, 2000. Focal accumulation of cyclooxygenase-1 (COS-1) and COX-2 expressing cells in cerebral malaria. J Neuroimmunol 106 : 198–205.
  7. Murakami M, Nakatani Y, Atsumi G, Inoue K, Kudo I, 1997. Regulatory functions of phospholipase A2. Crit Rev Immunol 17 : 225–283.
  8. Uozumi N, Kume K, Nagase T, Nokatani N, Ishii S, Tashiro F, Komagata Y, Maki K, Ikuta K, Ouchi Y, Miyazaki J, Shimizu T, 1997. Role of cytosolic phospholipase A2 in allergic response and parturition. Nature 390 : 618–622.
  9. Bonventre JV, Huang A, Taheri MR, O’Leary E, Li E, Moskowitz MA, Sapirstein A, 1997. Reduced fertility and postischaemic brain injury in mice deficient in cytosolic phopholipase A2. Nature 390 : 622–625.
  10. Nagase Y, Uozumi N, Ishii S, Kume K, Izumi T, Ouchi Y, Shimizu T, 2000. Acute lung injury by sepsis and acid aspiration: a key role for cytosolic phospholipase A2. Nature Immunol 1 : 42–46.
  11. Nogami S, Watanabe J, Nakagaki K, Nakata K, Suzuki H, Suzuki H, Fujisawa M, Kodama T, Kojima S, 1998. Involvement of macrophage scavenger receptors in protection against murine malaria. Am J Trop Med Hyg 59 : 843–845.
  12. Kishimoto K, Matsumura K, Kataoka Y, Morii H, Watanabe Y, 1999. Localization of cytosolic phospholipase A2 messenger RNA mainly in neurons in the rat brain. Neuroscience 92 : 1061–1077.
  13. Kurusu S, Motegi S, Kawaminami M, Hashimoto I, 1998. Expression and cellular distribution of cytosolic phospholipase A2 in the rat ovary. Prostaglandins Leukot Essent Fatty Acids 58 : 399–404.
  14. Murakami M, Kudo I, 2002. Phospholipase A2. J Biochem 131 : 285–292.
  15. Song C, Chang XJ, Bean KM, Proia MS, Knopf JL, Kriz RW, 1999. Molecular characteriation of cytosolic phopholipase A2-beta. J Biol Chem 274 : 17063–17067.
  16. Underwood KW, Song C, Kriz RW, Chang XJ, Knopf JL, Lin LL, 1998. A novel calcium-independent phospholipase A2, cPLA2-gamma, that is prenylated and contains homology to cPLA2. J Biol Chem 273 : 21926–21932.
  17. Koduri RS, Gronroos JO, Laine VJ, Le Calvez C, Lambeau G, Nevalainen TJ, Gelb MH, 2002. Bactericidal properties of human and murine groups I, II, V, X, and XII secreted phospholipases A(2). J Biol Chem 277 : 5849–5857.
  18. Vadas P, Keystone J, Stefanski E, Scott K, Pruzanski W, 1992. Induction of circulating group II phospholipase A2 expression in adults with malaria. Infect Immun 60 : 3928–3931.
  19. Vadas P, Taylor TE, Chimsuku L, Doldring D, Stefanski E, Pruzanski W, Molyneux ME, 1993. Increased serum phospholipase A2 in Malawian children with falciparum malaria. Am J Trop Med Hyg 49 : 455–459.
  20. Kennedy BP, Payette P, Mudgett J, Vadas P, Pruzanski W, Kwan M, Tang C, Rancourt DE, Cromlish WA, 1995. A natural disruption of the secretory group II phospholipase A2 gene in inbred mouse strains. J Biol Chem 270 : 22378–22385.
  21. Bagot S, Boubou MI, Campino S, Behrschmidt C, Gorgette O, Guenet JL, Penha-Goncalves C, Mazier D, Pied S, Cazenave PA, 2002. Susceptibility to experimental cerebral malaria induced by Plasmodium berghei ANKA in inbred mouse strains recently derived from wild stock. Infect Immun 70 : 2049–2056.
  22. Hanasaki K, Yokota Y, Ishizaki J, Itoh T, Arita H, 1997. Resistance to endotoxic shock in phospholipase A2 receptor-deficient mice. J Biol Chem 272 : 32792–32797.
  23. Yokota Y, Higashino K, Nakano K, Arita H, Hanasaki K, 2000. Identification of group X secretory phospholipase A2 as a natural ligand for mouse phospholipase A2 receptor. 2000. FEBS Lett 478 : 187–191.
  24. Morioka Y, Saiga A, Yokota Y, Suzuki N, Ikeda M, Ono T, Nakano K, Fujii N, Ishizaki J, Arita H, Hanasaki K, 2000. Mouse group X secretory phospholipase A2 induces a potent release of arachidonic acid from spleen cells and acts as a ligand for the phospholipase A2 receptor. Arch Biochem Biophys 381 : 31–42.
  25. Foote SJ, Burt RA, Baldwin TM, Presente A, Roberts AW, Laural YL, Lew AM, Marshall VM, 1997. Mouse loci for malaria-induced mortality and the control of parasitaemia. Nat Genet 17 : 380–381.
  26. Fortin A, Belouchi A, Tam MF, Cardon L, Skamene E, Stevenson MM, Gros P, 1997. Genetic control of blood parasitaemia in mouse malaria maps to chromosome 8. Nat Genet 17 : 382–383.
  27. Bagot S, Campino S, Penha-Goncalves C, Peid S, Cazevnave PA, Holmberg D, 2002. Identification of two cerebral malaria resistance loci using an inbred wild-derived mouse strain. Proc Natl Acad Sci USA 99 : 9919–9923.

Data & Media loading...

  • Received : 19 Mar 2003
  • Accepted : 02 Feb 2004

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error