title: NK cell-mediated killing of AML blasts: role of histamine, monocytes and reactive oxygen metabolites.
abstract: Blasts recovered from patients with acute myelogenous leukaemia (AML) were lysed by heterologous natural killer (NK) cells treated with NK cell-activating cytokines such as interleukin-2 (IL-2) or interferon-alpha (IFN-alpha). The cytokine-induced killing of AML blasts was inhibited by monocytes, recovered from peripheral blood by counterflow centrifugal elutriation. Histamine, at concentrations exceeding 0.1 microM, abrogated the monocyte-induced inhibition of NK cells; thereby, histamine and IL-2 or histamine and IFN-alpha synergistically induced NK cell-mediated destruction of AML blasts. The effect of histamine was completely blocked by the histamine H2-receptor (H2R) antagonist ranitidine but not by its chemical control AH20399AA. Catalase, a scavenger of reactive oxygen metabolites (ROM), reversed the monocyte-induced inhibition of NK cell-mediated killing of blast cells, indicating that the inhibitory signal was mediated by products of the respiratory burst of monocytes. It is concluded that (i) monocytes inhibit anti-leukemic properties of NK cells, (ii) the inhibition is conveyed by monocyte-derived ROM, and (iii) histamine reverses the inhibitory signal and, thereby, synergizes with NK cell-activating cytokines to induce killing of AML blasts.
authors.affiliation: Department of Medicine, Sahlgren's University Hospital, Göteborg, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Brune
authors.forename: M
authors.initials: M
authors.lastname: Hansson
authors.forename: U H
authors.initials: UH
authors.lastname: Mellqvist
authors.forename: S
authors.initials: S
authors.lastname: Hermodsson
authors.forename: K
authors.initials: K
authors.lastname: Hellstrand
mesh_terms: D019002:CD56 Antigen / Q000032:analysis; D002374:Catalase / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D006632:Histamine / Q000502:physiology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006801:Humans; D007111:Immunity, Cellular; D007167:Immunotherapy; D016898:Interferon-alpha / Q000502:physiology; D007376:Interleukin-2 / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology*; D015470:Leukemia, Myeloid, Acute / Q000276:immunology*; D009000:Monocytes / Q000502:physiology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D011899:Ranitidine / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000502:physiology; D011970:Receptors, Histamine H2 / Q000502:physiology; D014407:Tumor Cells, Cultured
chemical_list: D019002:CD56 Antigen; D006635:Histamine H2 Antagonists; D016898:Interferon-alpha; D007376:Interleukin-2; D017382:Reactive Oxygen Species; D011970:Receptors, Histamine H2; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006632:Histamine; D011899:Ranitidine; D002374:Catalase