Pharmacologic control of histamine release from human basophils induced by platelet- activating factor

Michele Columbo, Edward M. Horowitz, Jane McKenzie-White, Anne Kagey-Sobotka, Lawrence M. Lichtenstein

Research output: Contribution to journalArticle

Abstract

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 μM), dimaprit (1-100 μM) and dibuty- ryl 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 μΜ) potently inhibited histamine secretion activated by PAF, whereas SKF 95654 (PDE III inhibitor; 0.01-10 μΜ) was ineffective. The kinase inhibitor, staurosporine (0.1-100 nM), enhanced PAF-induced basophil histamine release, whereas the G-protein inhibitor, pertussis toxin (1 μg/ml), had an inhibitory effect. The specific lipoxygenase inhibitor, AA-861 (0.1-10 μM), inhibited PAF-activated histamine release, while the leukotriene A4 hydrolase inhibitor, bestatin (100 μΜ), had only a marginal effect. Finally, the Ca2+ channel entry blockers, verapamil (3-30 μΜ) and zinc (1.5-50 μΜ), inhibited PAF- induced histamine release. These results suggest that PAF is a unique secretagogue for human basophils unlike antigen, anti-IgE or univalent stimuli.

Original languageEnglish (US)
Pages (from-to)383-390
Number of pages8
JournalInternational Archives of Allergy and Immunology
Volume102
Issue number4
DOIs
StatePublished - Jan 1 1993

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Keywords

  • Anti-immunoglobulin E
  • Basophils
  • Histamine
  • Platelet-activating factor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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