Occupancy of platelet receptors for platelet-activating factor in asthmatic patients during an allergen-induced bronchoconstrictive reaction.
The administration of platelet-activating factor (PAF) to human subjects triggers asthma-like responses. We investigated whether a bronchoconstrictive reaction was accompanied by the release of PAF in the circulation of allergic asthmatics. The appearance of PAF was assessed by measuring the number of freely accessible PAF-receptors on platelets in vitro, assuming that the contact between platelets and PAF in vivo would reduce the receptor binding of [3H]PAF in vitro. 16 asthmatics were challenged twice, first with buffer and the next day with allergen. A comparison between receptor binding after provocation with the data of the same patients after allergen challenge revealed a significant difference in PAF binding (P = 0.034), with an average decrease of 14% immediately after allergen challenge followed by a return to control values after about 4 h and a transient increase of 9% at 7 h after provocation. The decrease in accessible PAF receptors was accompanied by a slight decrease in platelet count in peripheral blood between 30 min and 4 h after allergen challenge. The platelet counts recovered to the original values afterwards. These data support the concept that in patients with allergic asthma PAF is secreted in the circulation. The contact between PAF and the platelets may trigger the transient sequestration of platelets, possibly in the lung. Thus, PAF and platelets may contribute to the pathogenesis of allergic asthma.
Department of Hematology, University Hospital Utrecht, The Netherlands.
J A
JA
Burgers
P L
PL
Bruynzeel
H J
HJ
Mengelers
J
J
Kreukniet
J W
JW
Akkerman
D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000276:immunology*; D001249:Asthma / Q000097:blood* / Q000378:metabolism; D001665:Binding Sites; D001792:Blood Platelets / Q000378:metabolism* / Q000648:ultrastructure; D016084:Bronchoconstriction / Q000187:drug effects / Q000502:physiology*; D002021:Buffers; D004906:Erythrocyte Count; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D010972:Platelet Activating Factor / Q000378:metabolism; D015539:Platelet Activation; D010976:Platelet Count; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D012680:Sensitivity and Specificity; D014316:Tritium
D000485:Allergens; D002021:Buffers; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D014316:Tritium