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J Allergy Clin Immunol. 1999 Feb;103(2 Pt 1):289-97.

Production of chemokines and proinflammatory and antiinflammatory cytokines by human alveolar macrophages activated by IgE receptors.

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1
Unité INSERM U416, Institut Pasteur, Lille, France.

Abstract

BACKGROUND:

The alveolar macrophage (AM) expresses the low affinity IgE receptor and has the ability to produce not only several proinflammatory cytokines (TNF-alpha, IL-1, IL-6) but also antiinflammatory cytokines (IL-1 receptor antagonist [IL-lra], IL-10), chemokines (IL-8, monocyte chemotactic protein-1 [MCP-1]), and macrophage inflammatory protein-1alpha (MIP-1alpha).

OBJECTIVE:

The aim of this study was to evaluate the capacity of the AM from patients with allergic asthma and control subjects to produce chemokines and antiinflammatory versus proinflammatory cytokines after activation by IgE receptors and to define the role of CD23 in this activation.

METHODS:

AMs were collected by bronchoalveolar lavage from 13 patients with allergic asthma and 14 healthy subjects. Adherent AMs were activated either by the successive addition of IgE and anti-IgE or by monoclonal mouse IgG anti-CD23 or by a control monoclonal mouse antibody. TNF, IL-1beta, IL-1ra, IL-10, IL-8, MCP-1, and MIP-1alpha levels were evaluated in supernatants of AMs incubated for 18 hours and in some cases after 4 hours of incubation.

RESULTS:

Activation by IgE and anti-IgE antibodies significantly increased the production of TNF, IL-1beta, IL-8, MCP-1, MIP-lalpha, and IL-10 in both control subjects and patients with asthma, whereas the increase for IL-1ra was only significant for the control subjects. Whereas F(ab) fragments of anti-CD23 antibodies inhibited IgE plus anti-IgE-induced cytokine production, activation by monoclonal IgG anti-CD23 antibodies reproduced the effect of IgE immune complexes. At 4 hours, the secretion of proinflammatory cytokines was increased by activation by IgE receptors, in contrast to antiinflammatory cytokines. In addition, analysis of the balance between proinflammatory and antiinflammatory cytokines showed that IgE-dependent activation largely favored the proinflammatory cytokines, particularly in patients with asthma.

CONCLUSION:

IgE-dependent activation by the FcepsilonRII receptor upregulates the synthesis of both chemokines and antiinflammatory cytokines in addition to proinflammatory cytokines. However, AMs from patients with allergic asthma may promote airway inflammation after activation by IgE receptors through its preferential effect on proinflammatory cytokines.

PMID:
9949321
DOI:
10.1016/s0091-6749(99)70504-x
[Indexed for MEDLINE]

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