Lung Secretoglobin Scgb1a1 Influences Alveolar Macrophage-Mediated Inflammation and Immunity

Abstract

Alveolar macrophage (AM) is a mononuclear phagocyte key to the defense against respiratory infections. To understand AM's role in airway disease development, we examined the influence of Secretoglobin family 1a member 1 (SCGB1A1), a pulmonary surfactant protein, on AM development and function. In a murine model, high-throughput RNA-sequencing and gene expression analyses were performed on purified AMs isolated from mice lacking inScgb1a1gene and were compared with that from mice expressing the wild typeScgb1a1at weaning (4 week), puberty (8 week), early adult (12 week), and middle age (40 week). AMs from early adult mice underScgb1a1sufficiency demonstrated a total of 37 up-regulated biological pathways compared to that at weaning, from which 30 were directly involved with antigen presentation, anti-viral immunity and inflammation. Importantly, these pathways underScgb1a1deficiency were significantly down-regulated compared to that in the age-matchedScgb1a1-sufficient counterparts. Furthermore, AMs fromScgb1a1-deficient mice showed an early activation of inflammatory pathways compared with that fromScgb1a1-sufficient mice. Ourin vitroexperiments with AM culture established that exogenous supplementation of SCGB1a1 protein significantly reduced AM responses to microbial stimuli where SCGB1a1 was effective in blunting the release of cytokines and chemokines (including IL-1b, IL-6, IL-8, MIP-1a, TNF-a, and MCP-1). Taken together, these findings suggest an important role forScgb1a1in shaping the AM-mediated inflammation and immune responses, and in mitigating cytokine surges in the lungs.