FIGURE 7.

Proposed mechanism for myeloid cell‐derived Netrin‐1 during LPS‐induced acute lung injury. During acute lung injury initiated by intratracheal injection of LPS, macrophages are activated through toll‐like receptor 4. Netrin‐1 is expressed by activated macrophages via stabilization of the transcription factor, hypoxia inducible factor‐1 alpha (HIF‐1α), which binds to and activates the promoter of Netrin‐1. Myeloid‐derived Netrin‐1 plays a critical role in regulating chemokine (C‐C motif) ligand 2 (CCL2) and subsequently limits the recruitment of pro‐inflammatory natural killer (NK) cells. The ultimate effect of regulating NK cell accumulation by myeloid‐derived Netrin‐1 is to dampen inflammation, polymorphonuclear neutrophil (PMN) accumulation, and lung injury. Created with BioRender.com