Alveolar macrophages express membrane CD200 that inhibits mast cell activation

Abstract

Alveolar Macrophages are central regulators of pulmonary immune responses, yet their regulatory functions are misunderstood. CD200, a transmembrane protein, and its receptor (CD200R) play a critical role in the resolution of inflammation, but their role in asthma is still unclear. CD200 is expressed on many cell types such as leukocytes, T cells, B cells, epithelial cells, and endothelial cells, while CD200R is expressed exclusively on myeloid cells including alveolar macrophages (AM) and mast cells (MC), which play a key role in asthma. Recent study showed that leukocytes from asthmatic patients express lower level of CD200 during exacerbations, suggesting a dysregulation of CD200 pathway. Thus, we investigated the modulation of CD200 expression on AM following allergen challenge and the inhibition of MC functions by AM CD200. 
 Expression of CD200 and CD200R were measured on AM from naive and sensitized rats before and after allergen challenge using flow cytometry. AM modulation of antigen‐stimulated MC was investigated in vitro using co‐culture and MC degranulation and cytokine production.
 AM from naive and sensitized rats express similar level of CD200. However, allergen exposure increased CD200 expression on AM of naïve rats (that do not develop signs of asthma), but not on AM of sensitized rats (that develop experimental asthma). No difference between groups was observed for CD200R expression. Naive AM inhibited antigen‐stimulated MC degranulation and cytokine production. The addition of neutralizing anti‐CD200R antibody abrogated AM inhibitory effects. 
 These results suggest that modulation of CD200 expression on AM could have an important role in asthma regulation.