Pentraxins down-modulates M2 macrophages and protects against Fungal Spore-Induced Asthma.

A.P. Moreira, PhD1, D. Fong, BSC2, L. Lynne Murray, PhD3, D. Hesson, PhD3, R. Hullinger, BSC2, R.S. Rosada, MSC2, C.M. Hogaboam, Ph.D.2

Author address: 

1Ann Arbor, MI/US, 2Ann Arbor/US, 3Malvern/US

Abstract: 

Airborne Aspergillus fumigatus spores or conidia aggravate asthmatic responses. Lung resident macrophages are the first responders to fungal conidia but the presence of type-2 cytokines during asthma contributes to the preferential differentiation of alternatively activated (M2) macrophages, which exhibit increased secretion of pro-allergic factors. Considering that short pentraxins modulate macrophage function, we examined the effect of the short-pentraxins C-reactive protein (CRP) and serum amyloid P (SAP) in an experimental model of A. fumigatus-induced asthma. SAP potently inhibited the generation of M2 markers such as arginase and the chitinase Ym-1 via a FcgR-dependent mechanism in cultured macrophages. This effect correlated with a decrease in STAT6 phosphorylation in SAP-treated M2 macrophages. In vivo treatment with SAP, but not CRP decreased methacholine-induced bronchial responsiveness, eosinophilic inflammation, mucus cell metaplasia, and collagen deposition in mice with fungal asthma. Finally, the adoptive transfer of naí¯ve macrophages but not M2 macrophages into asthmatic mice significantly attenuated airway hyper-responsiveness and inflammation. Prior SAP treatment of M2 macrophages restored the inhibitory effect of these cells upon transfer into asthmatic mice. Collectively, these findings demonstrate that SAP is a potent inhibitor of M2 macrophage differentiation and represents a novel therapy in A. fumigatus-induced asthma. Am J Respir Crit Care Med 181;2010:A1288
2010

abstract No: 

Poster Board # D21

Full conference title: 

American Thoracic Society International Conference
    • ATS 2010