Role of pertussis toxin-sensitive G proteins in stimulus-dependent human eosinophil degranulation

H. Kita, R. I. Abu-Ghazaleh, G. J. Gleich, R. T. Abraham

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44 Scopus citations

Abstract

Stimulation of human normodense eosinophils with immobilized secretory IgA (sIgA) or IgG, or with the soluble stimulus, FMLP, triggers the exocytotic release of the granule protein, eosinophil-derived neurotoxin (EDN). In this report, we demonstrate that these stimuli also provoke an increase in phospholipase C-mediated phosphoinositide breakdown in eosinophils. Pretreatment of eosinophils with pertussis toxin (PTX) for 2 h irreversibly abolished the increases in phospholipase C activity and EDN release induced by immobilized sIgA or FMLP. In contrast, PTX treatment only transiently inhibited eosinophil activation induced by immobilized IgG. Maximal inhibition of IgG-stimulated phosphoinositide hydrolysis and EDN release occurred after 2 h of PTX pretreatment with PTX, followed by a gradual recovery of cellular responsiveness to immobilized IgG as the duration of PTX pretreatment was extended to 16 h. Activated PTX catalyzed the in vitro ADP- ribosylation of 41- and 44-kDa proteins in eosinophil membranes. A 2-h pretreatment of intact cells with PTX markedly reduced the pools of unmodified 41- and 44-kDa substrates available for subsequent ADP- ribosylation in vitro, suggesting that both proteins were substrates for PTX in intact eosinophils. Continuous exposure of eosinophils to PTX for times ranging from 2 to 15 h resulted in the gradual reappearance of unmodified 44- kDa protein, whereas the levels of unmodified 41-kDa protein were persistently reduced in PTX-treated cells. The time course of the decline and reapperance of unmodified 44-kDa substrate in PTX-treated eosinophils closely paralleled the changes in the responsiveness of these cells to immobilized IgG. These results suggest that the receptors for sIgA, FMLP, or IgG transduce activating signals for eosinophil degranulation through differential coupling to at least two PTX-sensitive G proteins.

Original languageEnglish (US)
Pages (from-to)3466-3473
Number of pages8
JournalJournal of Immunology
Volume147
Issue number10
StatePublished - Jan 1 1991

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Kita, H., Abu-Ghazaleh, R. I., Gleich, G. J., & Abraham, R. T. (1991). Role of pertussis toxin-sensitive G proteins in stimulus-dependent human eosinophil degranulation. Journal of Immunology, 147(10), 3466-3473.