Serum amyloid P attenuates M2 macrophage activation and protects against fungal spore-induced allergic airway disease.

Autor: Moreira AP; Immunology Program, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-2200, USA. anapaula@umich.edu, Cavassani KA, Hullinger R, Rosada RS, Fong DJ, Murray L, Hesson DP, Hogaboam CM
Jazyk: angličtina
Zdroj: The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2010 Oct; Vol. 126 (4), pp. 712-721.e7. Date of Electronic Publication: 2010 Jul 31.
DOI: 10.1016/j.jaci.2010.06.010
Abstrakt: Background: Aspergillus fumigatus conidia aggravate asthmatic responses. Lung macrophages normally kill fungal conidia, but the presence of type 2 cytokines during asthma contributes to the alternative (or M2) activation of these cells, which secrete proallergic factors and exhibit impaired innate immunity.
Objective: Considering that pentraxins modulate macrophage function, we examined the effect of C-reactive protein (CRP) and serum amyloid P (SAP) in an experimental model of A fumigatus-induced allergic airway disease.
Methods: The effects of SAP and CRP on M2 macrophage differentiation were examined in vitro, and the in vivo effects of these pentraxins were analyzed in the asthma model.
Results: SAP inhibited the generation of M2 markers, such as arginase and the chitinase Ym-1, through an FcγR-dependent mechanism in cultured macrophages. This effect correlated with a decrease in signal transducer and activator of transcription 6 (STAT6) phosphorylation in SAP-treated M2 macrophages. In vivo treatment with SAP significantly decreased methacholine-induced bronchial resistance, mucus cell metaplasia, the number of "found in inflammatory zone 1" (FIZZ1)-positive cells in the lungs, and collagen deposition compared with the control group. CRP had a modest effect on M2 differentiation, and in vivo treatment with CRP had a minor effect or exacerbated A fumigatus-induced lung disease. Finally, the adoptive transfer of SAP-pretreated M2 macrophages into allergic mice significantly attenuated disease when compared with nontransferred or M2-transferred control groups.
Conclusions: These findings demonstrate that SAP is a potent inhibitor of M2 macrophage differentiation and represents a novel therapy in A fumigatus-induced allergic disease.
(Copyright © 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)
Databáze: MEDLINE
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