Macrophage-epithelial interactions in pulmonary alveoli

Abstract

Alveolar macrophages have been investigated for years by approaches involving macrophage extraction from the lung by bronchoalveolar lavage, or by cell removal from lung tissue. Since extracted macrophages are studied outside their natural milieu, there is little understanding of the extent to which alveolar macrophages interact with the epithelium, or with one another to generate the lung's innate immune response to pathogen challenge. Here, we review new evidence of macrophage-epithelial interactions in the lung, and we address the emerging understanding that the alveolar epithelium plays an important role in orchestrating the macrophage-driven immune response.

Figure

Functional heterogeneity in sessile alveolar macrophages (SAMs). The upper figure shows a macrophage that forms gap junctional channels (GJCs) with the alveolar epithelium (right) and one that does not (left). LPS challenge induces secretion of proinflammatory cytokines from the macrophages, initiating alveolar inflammation. Ca²⁺ waves (red arrows) originate from the GJC-forming macrophage, then diffuse in the adjoining alveolar epithelium. The lower figure shows that GJC transmitted Ca²⁺ activates CAMKKα-induced signaling, inhibiting inflammatory signaling in the alveolar epithelium (AE). Pathogen sensing by sessile macrophages takes place as the alveolar wall liquid (AWL) convectively transports pathogens caught in alveolar surfactant towards the macrophages.