Potentiation of histamine release from human leucocytes by PAF

Studies on the effects of PAF on histamine release from human leucocytes have yielded conflicting results. We therefore investigated the effects of PAF on leucocytic histamine release (HR) focusing on direct as well as on modulating effects. Peripheral blood leucocytes of normal and atopic subjects were incubated with PAF, anti-IgE and FMP for 30 min at 37 degrees C, and histamine was measured fluorometrically. Unlike anti-IgE (1/2000) and FMP (10(-5) M) which caused histamine release (HR) of 34 +/- 7% and 31 +/- 8%, respectively, PAF by itself (10(-11)-10(-5) M) failed to induce any significant HR from human leucocytes (< 3%) in normal (n = 14) and atopic subjects (n = 6). Nevertheless, in normals as well as atopics, PAF, but not lyso-PAF, enhanced anti-IgE (1/2000) and FMP (10(-5) M)-induced HR in a concentration-related manner. Maximal potentiation of histamine release caused by FMP and anti-IgE was achieved with PAF (10(-7)) (mean +/- SEM: 26 +/- 5%, n = 5, p < 0.01) and PAF (10(-5)) (mean +/- SEM: 20 +/- 7%, n = 7, p < 0.05), respectively. This potentiation was suppressed by WEB2086 (10(-5) M), a specific PAF antagonist. The time course of the enhancing effect produced by PAF was dependent on the type of secretagogue. The enhancement was nearly maximal when PAF and FMP were added simultaneously to the leucocytes, whereas a preincubation of 20 min with PAF was required to get maximal enhancement with anti-IgE. The enhancing activity of PAF on HR induced by both anti-IgE and FMP was reversed by washing the cells after preincubation. While PAF enhancement of FMP-induced HR persisted on mononuclear cell fraction containing basophils, that of anti-IgE-induced HR was considerably reduced under these conditions.