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

J Allergy Clin Immunol. 2010 Oct;126(4):712-721.e7. doi: 10.1016/j.jaci.2010.06.010. Epub 2010 Jul 31.


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.

MeSH terms

  • Airway Remodeling
  • Animals
  • Aspergillosis, Allergic Bronchopulmonary / immunology
  • Aspergillosis, Allergic Bronchopulmonary / microbiology
  • Aspergillosis, Allergic Bronchopulmonary / prevention & control*
  • Aspergillus fumigatus / immunology*
  • Aspergillus fumigatus / physiology
  • Asthma / immunology
  • Asthma / microbiology
  • Asthma / prevention & control*
  • C-Reactive Protein / pharmacology
  • Cell Differentiation
  • Disease Models, Animal
  • Female
  • Humans
  • Macrophage Activation / drug effects*
  • Macrophage Activation / immunology
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / immunology
  • Macrophages, Alveolar / cytology
  • Macrophages, Alveolar / drug effects
  • Macrophages, Alveolar / immunology
  • Mice
  • Mice, Inbred C57BL
  • Serum Amyloid P-Component / administration & dosage
  • Serum Amyloid P-Component / pharmacology*
  • Spores, Fungal / immunology*


  • Serum Amyloid P-Component
  • C-Reactive Protein