Effect of H1-antagonist Dithiaden on human PMN-leukocyte aggregation and chemiluminescence is stimulus-dependent.
OBJECTIVE
Contradictory data published on histamine-PMN leukocyte interactions stimulated us to study to the role of histamine and H1-antagonist Dithiaden in generation of reactive oxygen species (ROS) and aggregation of human neutrophils.


METHODS
Whole blood or isolated PMN-leukocytes were exposed in a dose-dependent way to histamine or H1-antagonist Dithiaden and subsequently stimulated. Whole blood was stimulated with opsonised zymosan (OZ). Isolated cells were stimulated with membrane stimuli (OZ, N-formyl-methionyl-leucyl-phenylalanine--fMLP), or membrane bypassing stimuli (Ca2+-ionophore A23187, phorbol-myristate-acetate--PMA). The luminol-enhanced chemiluminescence (CL) was measured separately (whole blood) in a luminometer or simultaneously with neutrophil aggregation in a whole blood lumiaggregometer.


RESULTS
Depending on the concentration used, Dithiaden" was 1.5- to 25.0-times more effective in inhibiting activated CL of whole blood than histamine. In isolated neutrophils both histamine and Dithiaden inhibited OZ- and A23187-stimulated CL dose-dependently, with potentiation observed after stimulation with PMA and fMLP. Histamine did not alter aggregation with any of the stimuli tested. Dithiaden inhibited A23187-, OZ- and PMA-stimulated PMN-leukocytes but potentiated fMLP-induced aggregation of isolated neutrophils. Simultaneous application of Dithiaden and histamine abolished the effect of Dithiaden on fMLP-stimulated CL.


CONCLUSIONS
Dithiaden, depending on the stimuli applied, inhibited human neutrophils, both isolated or in whole blood, more markedly than histamine. The inhibition of aggregation and CL was dose- and stimulus-dependent. Histamine administered simultaneously abolished the effect of Dithiaden on fMLP-stimulated PMN-leukocytes. It seems likely that the interaction of Dithiaden with neutrophils operated both at an extra- and intracellular level.
Nosál
R
R
Institute of Experimental Pharmacology SAS, Bratislava, Slovak Republic. exfarano@savba.sk
Drábiková
K
K
Cíz
M
M
Lojek
A
A
Danihelová
E
E
D001582:Benzothiepins / Q000494:pharmacology*; D000001:Calcimycin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002449:Cell Aggregation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007476:Ionophores / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008163:Luminescent Measurements; D008165:Luminol; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015054:Zymosan / Q000037:antagonists & inhibitors / Q000494:pharmacology
D001582:Benzothiepins; D006634:Histamine H1 Antagonists; D007476:Ionophores; D017382:Reactive Oxygen Species; D000001:Calcimycin; C100170:dithiadene; D009240:N-Formylmethionine Leucyl-Phenylalanine; D008165:Luminol; D006632:Histamine; D015054:Zymosan; D013755:Tetradecanoylphorbol Acetate