Reactive oxygen metabolite production is inhibited by histamine and H1-antagonist dithiaden in human PMN leukocytes.
The study evaluated the distinction between extracellular and intracellular production of reactive oxygen metabolites (ROM) in isolated polymorphonuclear leukocytes (PMNL) stimulated with opsonised zymosan (OZ) and investigated its modulation by the endogenous mediator histamine (0.1-100 mumol/l) and by the H1-antagonist dithiaden (1-100 mumol/l). For this observation, a modified luminol and an isoluminol amplified chemiluminescence (CL) technique were used. Our results showed that PMNL activated with OZ responded with a respiratory burst accompanied by both extra- and intracellular generation of ROM. Histamine and dithiaden significantly decreased both the extra- and intracellular component of chemiluminescence stimulated with OZ. While dithiaden decreased both the extra- and intracellular part of CL with the same potency, histamine decreased preferentially the extracellular part of CL. The fact that histamine as well as the H1-antagonist dithiaden decreased the respiratory burst indicates that not only histamine receptors but also non-receptor mechanisms could be involved in the reduction of CL. Interaction with enzymes (NADPH-oxidase, myeloperoxidase, phospholipase A2) or interference with PMNL membrane structure may well result in reduction of the chemiluminescence signal.
Drábiková
Katarína
K
Institute of Experimental Pharmacology Slovak Academy of Sciences, Dúbravská cesta 9, 842 16 Bratislava, Slovak Republic. exfadrak@savba.sk
Nosál
Rado
R
Jancinová
Viera
V
Cíz
Milan
M
Lojek
Antonín
A
D000328:Adult; D001582:Benzothiepins / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D008163:Luminescent Measurements; D008165:Luminol / Q000031:analogs & derivatives* / Q000494:pharmacology; D008875:Middle Aged; D018375:Neutrophil Activation / Q000187:drug effects*; D009504:Neutrophils / Q000378:metabolism*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016897:Respiratory Burst; D013482:Superoxide Dismutase / Q000378:metabolism; D015054:Zymosan / Q000378:metabolism
D001582:Benzothiepins; D006634:Histamine H1 Antagonists; D017382:Reactive Oxygen Species; C032487:isoluminol; C100170:dithiadene; D008165:Luminol; D006632:Histamine; D015054:Zymosan; D002374:Catalase; D013482:Superoxide Dismutase