UNSPECIFIED (1991) INTERFERON-GAMMA INHIBITS SEROTONIN RELEASE FROM MOUSE PERITONEAL MAST-CELLS. EUROPEAN JOURNAL OF IMMUNOLOGY, 21 (10). pp. 2559-2564. ISSN 0014-2980

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Abstract

Conditioned medium (CM) from concanavalin A-activated mouse spleen cells inhibits antigen-induced 5-hydroxytryptamine (5-HT) release from mouse peritoneal mast cells when added for 24 or 48 h to cell cultures containing monoclonal IgE sensitizing antibody. We present the following evidence that the spleen cell-derived inhibitory factor is interferon-gamma (IFN-gamma): (a) CM from Con A-activated spleen cells and from Chinese hamster ovary (CHO) cells transfected with the murine (Mu)IFN-gamma-gene both produced a graded inhibition of 5-HT release when added to peritoneal cell cultures containing IgE and subsequently challenged with antigen; (b) the relative inhibitory potency of the two preparations corresponded to their relative IFN content as determined by antiviral bioassay; (c) the inhibitory activity of spleen cell CM and of CM from IFN-gamma gene-transfected CHO cells was abolished by treatment with a rat monoclonal MuIFN-gamma-neutralizing antibody, i.e. 5-HT release returned to control levels, and (d) a highly immunopurified preparation of recombinant MuIFN-gamma-retained the inhibitory activity, and was active at concentrations as low as 2 U/ml. The inhibitory activity of IFN-gamma-appeared to be a direct effect of the cytokine on mast cells, since CM generated for different time periods from unfractionated peritoneal cells treated with purified recombinant MuIFN-gamma contained no inhibitory activity other than IFN-gamma-itself, as demonstrated by neutralization of the cytokine with monoclonal antibody. Furthermore, purified recombinant MuIFN-gamma was equally active on mast cells enriched by density centrifugation up to 95% purity as on unfractionated peritoneal cells (1%-2% mast cells). Purified recombinant MuIFN-gamma-inhibited 5-HT release induced by a range of different cell activators, namely antigen, anti-IgE, compound 48/80 and calcium ionophore A23187. Hence inhibition is not specific to IgE-dependent activation of mast cells, but seems to be directed more generally at the secretory process of these cells.

Item Type:	Journal Article
Subjects:	Q Science > QR Microbiology > QR180 Immunology
Journal or Publication Title:	EUROPEAN JOURNAL OF IMMUNOLOGY
Publisher:	VCH PUBLISHERS INC
ISSN:	0014-2980
Date:	October 1991
Volume:	21
Number:	10
Number of Pages:	6
Page Range:	pp. 2559-2564
Publication Status:	Published
URI:	http://wrap.warwick.ac.uk/id/eprint/22430

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