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

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.

These findings demonstrate that SAP is a potent inhibitor of M2 macrophage differentiation and represents a novel therapy in A fumigatus-induced allergic disease.

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.

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.

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.