Figure 6.

Proposed mechanism of light-induced NETosis. (1) Riboflavin absorbs UVA and blue light and is excited to the triplet state. (2) Tryptophan or other substrates (e.g., HEPES-buffer, tyrosine) transfer electrons or protons to triplet-riboflavin, which leads to ROS production. (3) Extracellular ROS generation (e.g., H₂O₂/OH^· or O^.−₂) by excited riboflavin in the presence of reactive substrates is required for further progression of NET formation. Extracellular ROS is scavenged by Trolox or catalase/SOD. (4) Extracellular ROS most likely activates the translocation of granular enzymes like NE and MPO to the nucleus, which leads to the decondensation of chromatin. The activation of NE and MPO is mandatory for chromatin decondensation and can be inhibited by 4-ABAH and iNE. Citrullination by PAD enzymes can presumably enhance decondensation. (5) After full decondensation, cells release the NET.