Fig. 5.

NETosis—modulation by the respiratory system. The response of the respiratory system to infection is complex involving chemokine recruitment of neutrophils and monocytes into the lumen of the alveoli. The NETotic release of cytotoxic DNA–protein complexes with NE, MPO, LL37, and other neutrophil proteases increases mucus viscosity and contributes to lung epithelial damage, thereby perpetuating a vicious cycle of injury and inflammation. Innate immune surfactant proteins (also termed collectins) contribute in maintaining the lungs' homeostasis with minimal inflammation. NETs are removed by DNAse degradation and macrophage ingestion. A delicate equilibrium between NETosis and NET clearance is fundamental for the successful combating of infectious agents with minimum tissue damage. NE neutrophil elastase, MPO myeloperoxidase, LL37 cathelicidin, SP-A surfactant protein A, SP-D surfactant protein D, PMN polymorphonuclear neutrophil, Mφ macrophages. Adapted and modified from Chen et al. [81]