DOI: 10.1101/2023.05.24.541735

Sessile alveolar macrophage connexin-43 determines mechano-immunity in the lung

L.Mthunzi G. A. Gusarova M. N. Islam S. Bhattacharya J. Bhattacharya

摘要

Although lung immunity is pathogen induced, the immunity can also be induced by mechanical distortion of the lung. The causal basis of the lungs mechanosensitive immunity remains unclear. Here, through live optical imaging of mouse lungs, we show that alveolar stretch due to hyperinflation induced prolonged cytosolic Ca2+ increases in sessile alveolar macrophages (AMs). Knockout studies revealed that the Ca2+ increases resulted from Ca2+ diffusion from the alveolar epithelium to sessile AMs through connexin 43 (Cx43)-containing gap junctions. Lung inflammation and injury in mice exposed to injurious mechanical ventilation were inhibited by AM-specific Cx43 knockout, or AM-specific delivery of a calcium inhibitor. We conclude, Cx43 gap junctions and calcium mobilization in sessile AMs determine the lungs mechanosensitive immunity, providing a therapeutic strategy against hyperinflation-induced lung injury.

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