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 clinical importance are subject of controversy. We hypothesized that a functional assay could help to better analyze the actual concentrations in vivo because PAF may be released locally and is short-lived. An assay 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 microgram/ml and PAF 2.5 x 10(-8) M) in aggregation and release reaction and its absence after previous exposure to PAF at concentrations 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 allergen (inhalative provocation test; a reduction of the FEV1 by > 15% was considered positive). The lack of a synergistic response to collagen 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 patients with a positive inhalative provocation test but not in 3 patients with a negative response.(ABSTRACT TRUNCATED AT 250 WORDS)
Beer
J H
JH
Department of Medicine, University Hospital, Bern, Switzerland.
Wüthrich
B
B
von Felten
A
A
D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000503:physiopathology*; D001985:Bronchial Provocation Tests / Q000379:methods; D003094:Collagen / Q000494:pharmacology; D004357:Drug Synergism; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D010972:Platelet Activating Factor / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism; D001620:beta-Thromboglobulin / Q000378:metabolism
D010972:Platelet Activating Factor; D001620:beta-Thromboglobulin; D012701:Serotonin; D003094:Collagen