Fig. 8.

Diagram illustrating the proposed cellular cross talk between alveolar macrophages, iNKT cells, and ATII cells after lung I/R. I/R directly activates ATII epithelial cells via activation of NADPH oxidase (NOX2), to produce CXCL1. I/R also likely activates NOX2 in macrophages to induce TNF-α which subsequently induces CXCL1 production by ATII cells via NOX2 activation. In addition, I/R induces iNKT cell-produced IL-17 (possibly also involving NOX2), which synergistically enhances TNF-α-mediated CXCL1 production by ATII cells. CXCL1 secreted from ATII cells then potently initiates neutrophil infiltration and subsequent lung injury.