title: Regulation of neutrophil phagocytosis of Escherichia coli by antipsychotic drugs.
abstract: Antipsychotic drugs (APDs) have been used to ease the symptoms of schizophrenia. APDs have recently been reported to regulate the immune response. Our previous studies revealed that the atypical APDs risperidone and clozapine and the typical APD haloperidol can inhibit the phagocytic ability of macrophages. Our research next determined the effects of APDs on the phagocytic ability of neutrophils, which are the most abundant type of white blood cells in mammals. Here we provide evidence that clozapine and haloperidol can induce increased phagocytic uptake of Escherichia coli by differentiated HL-60 cells and by purified human neutrophils. Furthermore, clozapine and haloperidol can increase the myeloperoxidase activity and IL-8 production in neutrophils. Our results also show that clozapine can inhibit E. coli survival within differentiated HL-60 cells. Furthermore, clozapine and haloperidol are shown to enhance cell surface Mac-1 expression and the activated AKT signaling pathway in purified neutrophils exposed to E. coli. These results indicate that clozapine and haloperidol can increase the phagocytic ability of neutrophils by increasing AKT activation when cells are exposed to bacteria.
authors.affiliation: Department of Research, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, New Taipei City, Taiwan.
authors.forename: Mao-Liang
authors.initials: ML
authors.lastname: Chen
authors.affiliation: Department of Research, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, New Taipei City, Taiwan; Department of Life Science, Chinese Culture University, Shih Lin, Taipei, Taiwan.
authors.forename: Semon
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Microbiology, Immunology and Biopharmaceuticals, National Chiayi University, Chiayi, Taiwan.
authors.forename: Tzung-Chieh
authors.initials: TC
authors.lastname: Tsai
authors.affiliation: Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Lu-Kai
authors.initials: LK
authors.lastname: Wang
authors.affiliation: Department of Research, Taipei Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, New Taipei City, Taiwan. Electronic address: afu2215@gmail.com.
authors.forename: Fu-Ming
authors.initials: FM
authors.lastname: Tsai
mesh_terms: D014150:Antipsychotic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D003024:Clozapine / Q000494:pharmacology; D004926:Escherichia coli / Q000276:immunology; D018922:HL-60 Cells; D006220:Haloperidol / Q000494:pharmacology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D009195:Peroxidase / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects* / Q000276:immunology; D018967:Risperidone / Q000494:pharmacology
chemical_list: D014150:Antipsychotic Agents; D016209:Interleukin-8; D016177:Macrophage-1 Antigen; D009195:Peroxidase; D003024:Clozapine; D006220:Haloperidol; D018967:Risperidone
keywords: Clozapine; HL-60; Haloperidol; Neutrophils; Phagocytosis