Stimulus-dependence and time-course of histamine and leukotriene release from chopped and dispersed human lung tissue

The calcium ionophore A23187 and anti-human IgE provoked a dose-dependent release of histamine and cysteinyl-leukotrienes (LTC4, LTD4 and LTE4) from dispersed human lung cells. Optimal release of histamine peaked at 3 min after challenge whereas the release of cysteinyl-leukotrienes peaked at 30 min. The molar ratio between released histamine and cysteinyl-leukotrienes was approximately 100:1. The ionophore, but not anti-IgE caused additional formation of LTB4 in the dispersed cells or the chopped lung, indicating that this chemoattractant is formed from cells not primarily activated by IgE-dependent mechanisms. Indomethacin failed to alter release of histamine or leukotrienes from dispersed cells, whereas further inhibition of lipoxygenases by NDGA abolished leukotriene formation and reduced the release of histamine.