Regulation of Ig-induced eosinophil degranulation by adenosine 3′,5′-cyclic monophosphate

Hirohito Kita, Randa I. Abu-Ghazaleh, Gerald J. Gleich, Robert T. Abraham

Research output: Contribution to journalArticle

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Abstract

We have investigated the effects of cAMP on Ig-induced human eosinophil activation. Stimulation of human normodense eosinophils with IgG- or secretory IgA (sIgA)-coated Sepharose beads induced cellular degranulation, as measured by the release of the granule protein, eosinophil-derived neurotoxin (EDN). Pretreatment with cAMP analogs (N6,O2,-dibutyryl adenosine-3,′:5′ cyclic monophosphate; 8-bromoadenosine 3′:5′ cyclic monophosphate; or N6-benzoyladenosine 3′:5′ cyclic monophosphate) or cAMP phosphodiesterase-inhibitors (theophylline or isobutylmethyl xanthine (IBMX)) strongly inhibited Ig-induced human eosinophil degranulation. The β-adrenoceptor agonists, isoproterenol and salbutamol, induced relatively low level increases in intracellular cAMP, and weakly suppressed EDN release induced by IgG-coated beads. However, cellular pretreatment with IBMX synergistically enhanced the inhibitory effects of isoproterenol or salbutamol on both IgG and sIgA-induced eosinophil degranulation. Similarly, PGE2 treatment increased intracellular cAMP concentrations in eosinophils and correspondingly inhibited the Ig-dependent cellular degranulation response: co-incubation with IBMX further enhanced both effects of PGE2. Finally, cholera toxin, which irreversibly activates the stimulatory guanine nucleotide-binding protein linked to adenylyl cyclase, strongly inhibited the release of EDN from IgG- or sIgA-stimulated eosinophils. The time-dependent accumulation of cAMP in cholera toxin-treated cells closely paralleled the time courses of inhibition of IgG- and sIgA-induced EDN release after toxin exposure. These data indicate that the cAMP-dependent signal transduction mechanism in eosinophils exerts a negative modulatory effect on the cellular degranulation responses induced by sIgA or IgG. The inhibitory effects of cAMP on eosinophil activation may provide an important physiologic and a clinically relevant therapeutic mechanism for limiting the release of eosinophil-derived cytotoxic proteins during certain allergic or inflammatory responses in vivo.

Original languageEnglish (US)
Pages (from-to)2712-2718
Number of pages7
JournalJournal of Immunology
Volume146
Issue number8
StatePublished - Apr 15 1991

Fingerprint

Eosinophils
Adenosine
Secretory Immunoglobulin A
Eosinophil-Derived Neurotoxin
Immunoglobulin G
Xanthine
Albuterol
Cholera Toxin
Isoproterenol
Dinoprostone
Phosphodiesterase Inhibitors
Guanine Nucleotides
Theophylline
Adenylyl Cyclases
Sepharose
Adrenergic Receptors
Signal Transduction
Carrier Proteins
Proteins

ASJC Scopus subject areas

  • Immunology

Cite this

Kita, H., Abu-Ghazaleh, R. I., Gleich, G. J., & Abraham, R. T. (1991). Regulation of Ig-induced eosinophil degranulation by adenosine 3′,5′-cyclic monophosphate. Journal of Immunology, 146(8), 2712-2718.

Regulation of Ig-induced eosinophil degranulation by adenosine 3′,5′-cyclic monophosphate. / Kita, Hirohito; Abu-Ghazaleh, Randa I.; Gleich, Gerald J.; Abraham, Robert T.

In: Journal of Immunology, Vol. 146, No. 8, 15.04.1991, p. 2712-2718.

Research output: Contribution to journalArticle

Kita, H, Abu-Ghazaleh, RI, Gleich, GJ & Abraham, RT 1991, 'Regulation of Ig-induced eosinophil degranulation by adenosine 3′,5′-cyclic monophosphate', Journal of Immunology, vol. 146, no. 8, pp. 2712-2718.
Kita, Hirohito ; Abu-Ghazaleh, Randa I. ; Gleich, Gerald J. ; Abraham, Robert T. / Regulation of Ig-induced eosinophil degranulation by adenosine 3′,5′-cyclic monophosphate. In: Journal of Immunology. 1991 ; Vol. 146, No. 8. pp. 2712-2718.
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