Effect of H-1-antagonist Dithiaden((R)) on human PMN-leukocyte aggregation and chemiluminescence is stimulus-dependent
Objective and design: Contradictory data published on histamine-PMN leukocyte interactions stimulated us to study to the role of histamine and H-1-antagonist Dithiaden((R)) in generation of reactive oxygen species (ROS) and aggregation of human neutrophils. Methods and materials: Whole blood or isolated PMN-leukocytes were exposed in a dose-dependent way to histamine or H-1-antagonist Dithiaden((R)) 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 A23 187, 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, Dithiadene 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((R)) 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. Dithiadene inhibited A23187-, OZ- and PMA-stimulated PMN-leukocytes but potentiated fmLP-induced aggregation of isolated neutrophils. Simultaneous application of Dithiaden((R)) and histamine abolished the effect of Ditbiaden((R)) on fMLP-stimulated CL. Conclusions: Dithiaden((R)), 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((R)) on fMLP-stimulated PMN-leukocytes. It seems likely that the interaction of Dithiaden((R)) with neutrophils operated both at an extra- and intracellular level.