Histamine inhibits neutrophil NADPH oxidase activity triggered by the lipoxin A4 receptor-specific peptide agonist Trp-Lys-Tyr-Met-Val-Met.
The vasoactive amine histamine is found at high concentrations in the immune and inflammatory tissues. Earlier studies have revealed that histamine regulates the nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase-dependent formation of oxygen radicals by phagocytic cells. However, the effects of histamine on intracellular signal transduction mechanisms of relevance to oxidase regulation remain controversial. For this study, we investigated the effects of histamine on NADPH oxidase activity in human neutrophil granulocytes triggered by a lipoxin A4 receptor agonist [the hexapeptide Trp-Lys-Tyr-Met-Val-Met (WKYMVM), a formyl peptide receptor (FPR) agonist (the chemotactic tripeptide formylmethionyl-leucyl-phenylalanine (fMLF)) and an activator of protein kinase C (phorbol myristate acetate (PMA)]. We report that histamine, acting via H2-type histamine receptors (H2R), suppresses NADPH oxidase-dependent formation of oxygen radicals induced by WKYMVM and fMLF but not that induced by PMA. Peptide-induced mobilization of granule-localized complement receptor 3 (CR3) was unaffected by histamine suggesting that the inhibition specifically affected NADPH oxidase activation. Our data suggest that histamine downregulates FPRL1- and FPR-induced NADPH oxidase activity upstream of protein kinase C (PKC) and downstream of the separation of the peptide-induced signal into granule secretion and oxidase activation.
Betten
A
A
Department of Virology, Göteborg University, Göteborg, Sweden. aasa.betton@microbio.gu.se
Dahlgren
C
C
Hermodsson
S
S
Hellstrand
K
K
D002630:Chemotactic Factors / Q000276:immunology / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000276:immunology; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000276:immunology / Q000494:pharmacology; D006632:Histamine / Q000276:immunology / Q000494:pharmacology*; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000276:immunology / Q000494:pharmacology; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D009842:Oligopeptides / Q000276:immunology / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000819:agonists* / Q000276:immunology; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; D015398:Signal Transduction / Q000187:drug effects; D013481:Superoxides / Q000276:immunology / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000276:immunology / Q000494:pharmacology
D002630:Chemotactic Factors; D004791:Enzyme Inhibitors; C105101:FPR2 protein, human; D009842:Oligopeptides; D011956:Receptors, Cell Surface; D044042:Receptors, Formyl Peptide; D044067:Receptors, Lipoxin; C113617:Trp-Lys-Tyr-Met-Val-Met; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D006632:Histamine; D019255:NADPH Oxidases; D013755:Tetradecanoylphorbol Acetate