ALLERGEN EXPOSURE IN ACUTE ASTHMA CAUSES THE RELEASE OF PLATELET-ACTIVATING-FACTOR (PAF) AS DEMONSTRATED BY THE DESENSITIZATION OF PLATELETS TO PAF

Platelet-activating factor (PAF) is released in IgE-mediated allergic diseases. The normal level, the method of its determination and its cl inical importance are subject of controversy. We hypothesized that a f unctional assay could help to better analyze the actual concentrations in vivo because PAF may be released locally and is short-lived. An as say to detect PAF by the desensitized state of human platelets exposed to PAF in vitro or ex vivo was developed: We analyzed the synergistic platelet response to dual agonist stimulation at extraordinarily low doses (collagen 0.10 mu g/ml and PAF 2.5 x 10(-8) M) in aggregation an d release reaction and its absence after previous exposure to PAF at c oncentrations between 5 x 10(-9) and 5 x 10(-11) M in vitro. The same test was then applied to examine the platelets from patients with IgE- mediated allergic asthma before and after inhalation of the specific a llergen (inhalative provocation test; a reduction of the FEV(1) by >15 % was considered positive). The lack of a synergistic response to coll agen with PAF was found after preincubation of the platelets with 5 x 10(-9) M PAF and a reduction of +/- 50% with 5 x 10(-10) M in vitro. A significant reduction of the aggregation response (-56+/-18%) and of the release of beta-thromboglobulin (-75+/-24%) was found in 6 patient s with a positive inhalative provocation test but not in 3 patients wi th a negative response. We conclude that PAF is released in asthma in man at levels of similar to 10(-10) M after challenge with the specifi c allergen and induces a desensitization of the platelets to PAF This mechanism may explain the platelet activation in asthma observed earli er and our assay may provide a useful diagnostic tool to document the release of PAF in vivo.