Pharmacologic control of histamine release from human basophils induced by platelet-activating factor.
We studied the effect of several compounds that influence different cell activation steps on platelet-activating factor (PAF)-induced basophil histamine secretion. Isobutylmethylxanthine (1-100 microM), dimaprit (1-100 microM) and dibutyryl adenosine 3',5'-cyclic phosphate (cAMP; 0.01-1 mM), that increase intracellular cAMP levels, concentration-dependently inhibited PAF-elicited histamine release. Rolipram (phosphodiesterase, PDE, isotype IV inhibitor; 0.1 nM-10 microM) potently inhibited histamine secretion activated by PAF, whereas SKF95654 (PDE III inhibitor; 0.01-10 microM) was ineffective. The kinase inhibitor, staurosporine (0.1-100 nM), enhanced PAF-induced basophil histamine release, whereas the G-protein inhibitor, pertussis toxin (1 microgram/ml), had an inhibitory effect. The specific lipoxygenase inhibitor, AA-861 (0.1-10 microM), inhibited PAF-activated histamine release, while the leukotriene A4 hydrolase inhibitor, bestatin (100 microM), had only a marginal effect. Finally, the Ca2+ channel entry blockers, verapamil (3-30 microM) and zinc (1.5-50 microM), inhibited PAF-induced histamine release. These results suggest that PAF is a unique secretagogue for human basophils unlike antigen, anti-IgE or univalent stimuli.
Columbo
M
M
Division of Clinical Immunology, Johns Hopkins University School of Medicine, Johns Hopkins Asthma and Allergy Center, Baltimore, Md.
Horowitz
E M
EM
McKenzie-White
J
J
Kagey-Sobotka
A
A
Lichtenstein
L M
LM
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D001491:Basophils / Q000187:drug effects / Q000276:immunology*; D000242:Cyclic AMP / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D037342:Pertussis Toxin; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000276:immunology*; D014700:Verapamil / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D004791:Enzyme Inhibitors; D010972:Platelet Activating Factor; D010566:Virulence Factors, Bordetella; D014700:Verapamil; D000242:Cyclic AMP; D037342:Pertussis Toxin; D015056:1-Methyl-3-isobutylxanthine