title: Short report: Lethal malaria in cytosolic phospholipase A2- and phospholipase A2IIA-deficient mice.
abstract: Lipid mediators play important roles in the pathogenesis of malaria. Phospholipase A2s are enzymes involved in the production of these mediators, and they function in inflammation. Among them, cytosolic phospholipase A2 (cPLA2) is a key enzyme in the metabolism of arachidonic acid, the first intermediate in the production of lipid mediators. Plasmodium berghei ANKA causes cerebral malaria in CL57B/6 mice, and we recently produced cPLA2-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 PLA2s rather than cPLA2 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 A2s in malaria.
authors.affiliation: Department of Pathology, The University of Tokyo, Hongo, Tokyo, Japan.
authors.forename: Shumpei
authors.initials: S
authors.lastname: Ishikawa
authors.forename: Naonori
authors.initials: N
authors.lastname: Uozumi
authors.forename: Takashi
authors.initials: T
authors.lastname: Shiibashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Izumi
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
authors.forename: Takao
authors.initials: T
authors.lastname: Shimizu
authors.forename: Junichi
authors.initials: J
authors.lastname: Watanabe
authors.forename: Sadao
authors.initials: S
authors.lastname: Nogami
mesh_terms: D000818:Animals; D003600:Cytosol / Q000201:enzymology*; D005260:Female; D054501:Group II Phospholipases A2; D016779:Malaria, Cerebral / Q000201:enzymology / Q000401:mortality* / Q000469:parasitology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018512:Parasitemia / Q000201:enzymology / Q000401:mortality; D010741:Phospholipases A / Q000235:genetics* / Q000378:metabolism; D054467:Phospholipases A2; D010962:Plasmodium berghei
chemical_list: D010741:Phospholipases A; D054501:Group II Phospholipases A2; D054467:Phospholipases A2