Pro-apoptotic effect of high concentrations of histamine on human neutrophils

International Immunopharmacology
Jun HurJong-Young Kwak


Histamine receptors are expressed on neutrophils, and therefore, are likely to modulate neutrophil function. In this study, we investigated whether histamine modulates human neutrophil survival. Neutrophils were found to rapidly undergo spontaneous apoptosis upon culture in vitro and this was accelerated by high concentrations of histamine. Moreover, the percentage of apoptotic neutrophils was also markedly increased by treating with 10 mM histamine in the presence of inflammatory mediators, such as lipopolysaccharide (LPS), granulocyte macrophage-colony stimulating factor (GM-CSF), dibutyryl-cAMP (db-cAMP), or dexamethasone. Histamine-induced neutrophil apoptosis was inhibited by pyrilamine, a histamine receptor 1 antagonist, and by ranitidine, a selective histamine receptor 2 antagonist. In addition, diphenylene iodonium (DPI), an inhibitor of NADPH-oxidase, significantly blocked the apoptotic effect of histamine. Moreover, the induction of apoptosis by histamine was almost completely inhibited by zVAD-fmk, a pan-caspase inhibitor. In addition, immunoblotting showed that histamine induced the proteolytic activation of procaspase-3 in cell lysates treated with histamine. And, the protein kinase C (PKC)-delta inhibitor, rottler...Continue Reading


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