title: [Role of histamine and histamine receptors in the pathogenesis of malaria].
abstract: A hallmark of the host response to Plasmodium parasite is an inflammatory reaction characterized by elevated histaminemia levels. Since histamine, which acts through four different receptors and which synthesis is under the control of the histidine decarboxylase (HDC), is endowed with pro-inflammatory and immunosuppressive activities, we hypothesized that this vaso-active amine may participe to malaria pathogenesis. Combining genetic and pharmacologic approaches by using H1R(-/-), H2R(-/-), H3R(-/-), HDC(-/-) mice and H1R, H2R-, and H3R-antagonists, respectively, we found that cerebral malaria-associated pathogenetic processes such as blood brain barrier disruption, and T lymphocyte sequestration to cerebral vascular endothelium in mice were associated with histamine production. The identification of this novel inflammatory pathway and its implication in Plasmodium infection may lead to novel strategies to manipulate the anti-Plasmodium immune response and may provide new therapeutic tools to alleviate malaria disease.
authors.affiliation: Unité de Biologie des Interactions hôte-parasite, Institut Pasteur, 75015 Paris, France.
authors.forename: Walid
authors.initials: W
authors.lastname: Beghdadi
authors.forename: Adeline
authors.initials: A
authors.lastname: Porcherie
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Schneider
authors.forename: David
authors.initials: D
authors.lastname: Dubayle
authors.forename: Roger
authors.initials: R
authors.lastname: Peronet
authors.forename: Michel
authors.initials: M
authors.lastname: Huerre
authors.forename: Takeshi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohtsu
authors.forename: Jacques
authors.initials: J
authors.lastname: Louis
authors.forename: Salah
authors.initials: S
authors.lastname: Mécheri
mesh_terms: D000328:Adult; D000818:Animals; D001491:Basophils / Q000502:physiology; D001812:Blood-Brain Barrier / Q000502:physiology; D002675:Child, Preschool; D006632:Histamine / Q000097:blood / Q000172:deficiency / Q000502:physiology*; D006638:Histidine Ammonia-Lyase / Q000172:deficiency / Q000502:physiology; D006790:Host-Parasite Interactions; D006801:Humans; D007223:Infant; D008288:Malaria / Q000503:physiopathology*; D016779:Malaria, Cerebral / Q000503:physiopathology; D016778:Malaria, Falciparum / Q000503:physiopathology; D008407:Mast Cells / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D018512:Parasitemia / Q000503:physiopathology; D010962:Plasmodium berghei; D011968:Receptors, Histamine / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D011968:Receptors, Histamine; D006632:Histamine; D006638:Histidine Ammonia-Lyase