Figure 2.

Integration of surfactant function and innate host defenses in the alveoli. Gas exchange is mediated by the close apposition of type I and type II epithelial cells to the endothelial cells of pulmonary capillaries, which creates an extensive surface area whereon environmental gases create collapsing forces at the hydrated surfaces of the alveoli (a,b). Hopx is a transcription factor selectively expressed in type I cells, and ABCA3 is a surfactant lipid transporter specific for type II epithelial cells in the alveoli (b). Antibody to smooth muscle actin (α-SMA) stains bronchiolar and vascular smooth muscle. Surface tension is diminished by pulmonary surfactant lipids and proteins secreted by type II epithelial cells (c–e) that remain stable during the dynamic compression and expansion of the lungs during ventilation. The biophysical activities of surfactant are integrated with alveolar host-defense functions that are mediated by the structural components of surfactant that have intrinsic antimicrobial activity. Tubular myelin (a,f), formed by surfactant proteins SP-A and SP-B, and lipid create a highly structured reservoir of surfactant and host-defense proteins that interact with alveolar macrophages and other cells of the immune system to bind to and remove microbial pathogens and ‘instruct’ inflammatory cells to mount appropriate host-defense responses (b). Alveolar epithelial cell and alveolar macrophages directly interact via Cnx43 channels to modify local inflammatory signals and regulate the expression of cytokines and chemokines in response to pathogens. The sizes of surfactant pools are maintained by the synthesis, secretion and reuptake of lipids and proteins by alveolar epithelial cells and by the catabolic activities of alveolar macrophages via processes regulated by GM-CSF that together maintain near sterility of the alveoli (a).