POTENTIATION OF HISTAMINE-RELEASE FROM HUMAN-LEUKOCYTES BY PAF

Studies on the effects of PAF on histamine release from human leucocyt es have yielded conflicting results. We therefore investigated the eff ects 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 m in at 37 degrees C, and histamine was measured fluorometrically. Unlik e 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)-1 0(-5) M) failed to induce any significant HR from human leucocytes (< 3%) in normal (n = 14) and atopic subjects (n = 6). Nevertheless, in n ormals 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), resp ectively. This potentiation was suppressed by WEB2086 (10(-5) M), a sp ecific PAF antagonist. The time course of the enhancing effect produce d by PAF was dependent on the type of secretagogue. The enhancement wa s nearly maximal when PAF and FMP were added simultaneously to the leu cocytes, whereas a preincubation of 20 min with PAF was required to ge t 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-i nduced HR was considerably reduced under these conditions. Further, pr eincubation of mononuclear cells containing basophils with the superna tant of granulocytes stimulated by PAF resulted in a stronger potentia tion of immunological histamine release than that afforded by the sole PAF on the mononuclear cell fraction. We conclude that PAF appears to be more an enhancing rather than a triggering agent for the basophil degranulation. The mechanism of this enhancing effect is different acc ording to the secretagogue and probably involves an intermediate media tor regarding immunologically induced histamine release.