The mechanism of mediator release from human basophils induced by platelet-activating factor

Michele Columbo, Vincenzo Casolaro, Jane A. Warner, Donald W. Macglashan, Anne Kagey-Sobotka, Lawrence M. Lichtenstein

Research output: Contribution to journalArticle

Abstract

Platelet-activating factor (PAF) is a lipid mediator able to induce a variety of inflammatory processes in human peripheral blood cells. We have investigated the effect of PAF on the release of chemical mediators from human basophils of allergic and normal donors. PAF (10 nM to 1 μM) caused a concentration-dependent, noncytotoxic histamine release (≥10% of total) in 27 of 44 subjects tested (24 atopic and 20 nonatopic donors). The release process was either very rapid (t1/2 ≅ 10 s) or quite slow (t1/2, ≅ 10 min), temperature- and Ca2+-dependent (optimal at 37°C and 5 mM Ca2+). Coincubation of PAF with cytochalasin B (5 μg/ml) enhanced the release of histamine induced by PAF and activated the release process in most donors (42 of 44). Atopies did not release significantly more histamine than normal subjects, and the percentage of PAF responders (≥10% of total) was nearly the same in the two groups. Histamine release was accompanied by the synthesis and release of leukotriene C4, although this lagged 1 to 2 min behind histamine secretion. Lyso-PAF (100 nM to 10 μM), alone or together with cytochalasin B, did not release significant amounts of histamine. The release of histamine activated by PAF was inhibited by the specific PAF receptor antagonist, L-652,731, with an IC50 of 0.4 μM. There was a partial desensitization to PAF when the cells were preincubated with PAF (100 nM to 1 μM) for 2 min in the absence of Ca2+, whereas the cells remained responsive to anti-IgE (0.1 μg/ml). If neutrophils were removed from the basophil preparation by a Percoll gradient or a countercurrent elutriation technique, there was a significant decrease in PAF-induced histamine release. PAF (1 μM) was able to induce a very rapid, transient rise (peak < 10 s) in [Ca2+]i in purified basophils analyzed by digital video microscopy. Finally, among human histamine-containing cells, the basophils are unique in degranulating following a PAF challenge. Mast cells from human lung, skin, or uterus failed to respond to PAF (10 nM to 1 μM) regardless of the presence or absence of cytochalasin B (5 μg/ml). Our results demonstrate that PAF is able to induce the release of inflammatory mediators from human basophils, and that neutrophils can influence this response. It is suggested that PAF-induced basophil activation can play a role in the pathogenesis of allergic disorders.

Original languageEnglish (US)
Pages (from-to)3855-3861
Number of pages7
JournalJournal of Immunology
Volume145
Issue number11
StatePublished - Dec 1 1990

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Columbo, M., Casolaro, V., Warner, J. A., Macglashan, D. W., Kagey-Sobotka, A., & Lichtenstein, L. M. (1990). The mechanism of mediator release from human basophils induced by platelet-activating factor. Journal of Immunology, 145(11), 3855-3861.