期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 126, 期 4, 页码 712-U75出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2010.06.010
关键词
Asthma; Aspergillus fumigatus; fungal-induced allergic airway disease; pentraxins; serum amyloid P component; macrophage; airway remodeling
资金
- Promedior
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 Fc gamma R-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. (J Allergy Clin Immunol 2010;126:712-21.)
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