The Journal of Immunology, Vol 146, Issue 8 2712-2718, Copyright © 1991 by American Association of Immunologists

ARTICLES

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

H Kita, RI Abu-Ghazaleh, GJ Gleich and RT Abraham
Department of Immunology, Mayo Graduate School of Medicine, Rochester, MN 55905.

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 beta-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.

This article has been cited by other articles:

				H. Sandig, J. E. Pease, and I. Sabroe Contrary prostaglandins: the opposing roles of PGD2 and its metabolites in leukocyte function J. Leukoc. Biol., February 1, 2007; 81(2): 372 - 382. [Abstract] [Full Text] [PDF]

				H. Tanaka, S. Kanako, and S. Abe Prostaglandin E2 Receptor Selective Agonists E-Prostanoid 2 and E-Prostanoid 4 May Have Therapeutic Effects on Ovalbumin-Induced Bronchoconstriction Chest, November 1, 2005; 128(5): 3717 - 3723. [Abstract] [Full Text] [PDF]

				G. Monneret, S. Gravel, M. Diamond, J. Rokach, and W. S. Powell Prostaglandin D2 is a potent chemoattractant for human eosinophils that acts via a novel DP receptor Blood, September 15, 2001; 98(6): 1942 - 1948. [Abstract] [Full Text] [PDF]

				S. LIM, K. TOMITA, G. CARRAMORI, A. JATAKANON, B. OLIVER, A. KELLER, I. ADCOCK, K. F. CHUNG, and P. J. BARNES Low-dose Theophylline Reduces Eosinophilic Inflammation but Not Exhaled Nitric Oxide in Mild Asthma Am. J. Respir. Crit. Care Med., July 15, 2001; 164(2): 273 - 276. [Abstract] [Full Text] [PDF]

				K. Yasui, K. Agematsu, K. Shinozaki, S. Hokibara, H. Nagumo, S. Yamada, N. Kobayashi, and A. Komiyama Effects of theophylline on human eosinophil functions: comparative study with neutrophil functions J. Leukoc. Biol., August 1, 2000; 68(2): 194 - 200. [Abstract] [Full Text]

				T. V. HARTERT, R. T. DWORSKI, B. G. MELLEN, J. A. OATES, J. J. MURRAY, and J. R. SHELLER Prostaglandin E2 Decreases Allergen-stimulated Release of Prostaglandin D2 in Airways of Subjects with Asthma Am. J. Respir. Crit. Care Med., August 1, 2000; 162(2): 637 - 640. [Abstract] [Full Text] [PDF]

				G. T. Kampen, S. Stafford, T. Adachi, T. Jinquan, S. Quan, J. A. Grant, P. S. Skov, L. K. Poulsen, and R. Alam Eotaxin induces degranulation and chemotaxis of eosinophils through the activation of ERK2 and p38 mitogen-activated protein kinases Blood, March 15, 2000; 95(6): 1911 - 1917. [Abstract] [Full Text] [PDF]

				M. A. Giembycz and M. A. Lindsay Pharmacology of the Eosinophil Pharmacol. Rev., June 1, 1999; 51(2): 213 - 340. [Abstract] [Full Text] [PDF]

				G. M. GAUVREAU, R. M. WATSON, and P. M. O'BYRNE Protective Effects of Inhaled PGE2 on Allergen-induced Airway Responses and Airway Inflammation Am. J. Respir. Crit. Care Med., January 1, 1999; 159(1): 31 - 36. [Abstract] [Full Text]

				C. I. Ezeamuzie and M. Al-Hage Differential Effects of Salbutamol and Salmeterol on Human Eosinophil Responses J. Pharmacol. Exp. Ther., January 1, 1998; 284(1): 25 - 31. [Abstract] [Full Text]