title: Human neutrophil-derived histamine-releasing activity (HRA-N) causes the release of serotonin but not arachidonic acid metabolites from rat basophilic leukemia cells.
abstract: The effects of neutrophil-derived histamine-releasing activity (HRA-N) on arachidonic acid (AA) metabolism is unknown. Human basophils exposed to HRA-N released 25% of total histamine but no leukotriene C4 (LTC4). To confirm this phenomenon, rat basophilic leukemia (RBL) cells were exposed to HRA-N as well as anti-IgE, or calcium ionophore A23187. RBL cells incubated with A23187 released 44% of available serotonin and 59 and 124 pmol/10(6) cells of prostaglandin D2 (PGD2) and LTC4, respectively. Anti-IgE stimulation resulted in 34% serotonin release and the generation of 34 pmol PGD2 per 10(6) cells and 72 pmol LTC4 per 10(6) cells. In contrast, HRA-N (2 U/ml) induced 20% serotonin release, 4 pmol PGD2 per 10(6) cells, and 0.6 pmol LTC4 per 10(6) cells. Neither increasing the dose nor the incubation time of HRA-N enhanced the generation of AA metabolite. Additionally, the spectrum of AA metabolites generated by RBL cells in response to those agents was examined by reverse-phase high-performance liquid chromatography. RBL cells stimulated with A23187 released PGD2, LTB4, and its isomers, LTC4, and 5-hydroxyeicosatetraenoic acid. In contrast, HRA-N stimulation resulted in only minimal PGD2 generation and no other discernable AA metabolites. Thus, HRA-N causes selective release of serotonin without inducing AA metabolites. These data suggest that HRA-N activates mast cells through a unique pathway.
authors.affiliation: Allergic Diseases Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md 20892.
authors.forename: Y
authors.initials: Y
authors.lastname: Igarashi
authors.forename: J D
authors.initials: JD
authors.lastname: Lundgren
authors.forename: M E
authors.initials: ME
authors.lastname: Doerfler
authors.forename: J H
authors.initials: JH
authors.lastname: Shelhamer
authors.forename: M A
authors.initials: MA
authors.lastname: Kaliner
authors.forename: M V
authors.initials: MV
authors.lastname: White
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D016718:Arachidonic Acid / Q000032:analysis / Q000378:metabolism*; D001491:Basophils / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D014408:Biomarkers, Tumor; D000001:Calcimycin / Q000494:pharmacology; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods; D006636:Histamine Release / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D015471:Leukemia, Basophilic, Acute / Q000378:metabolism*; D008222:Lymphokines / Q000032:analysis / Q000302:isolation & purification / Q000494:pharmacology*; D009504:Neutrophils / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D012701:Serotonin / Q000032:analysis / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D000090324:Tumor Protein, Translationally-Controlled 1
chemical_list: D000888:Antibodies, Anti-Idiotypic; D014408:Biomarkers, Tumor; D008222:Lymphokines; D000090324:Tumor Protein, Translationally-Controlled 1; C026408:anti-IgE antibodies; D016718:Arachidonic Acid; D012701:Serotonin; D007073:Immunoglobulin E; D000001:Calcimycin