NETosis Is Induced by Complement Component 5a: Implications in the Pathogenesis of Pyoderma Gangrenosum

NETosis is a host antimicrobial mechanism through the release of chromatin DNA and proteases ( Brinkmann et al., 2004 Brinkmann V. Reichard U. Goosmann C. Fauler B. Uhlemann Y. Weiss D.S. et al. Neutrophil extracellular traps kill bacteria. Science. 2004; 303: 1532-1535 Crossref PubMed Scopus (6488) Google Scholar ) that contribute to tissue damage and inflammation ( Wong et al., 2015 Wong S.L. Demers M. Martinod K. Gallant M. Wang Y. Goldfine A.B. et al. Diabetes primes neutrophils to undergo NETosis, which impairs wound healing. Nat. Med. 2015; 21: 815-819 Crossref PubMed Scopus (671) Google Scholar ). NETosis has been implicated in the pathogenesis of human diseases with sterile inflammation including Pyoderma gangrenosum (PG)( Croia et al., 2021 Croia C. Dini V. Loggini B. Manni E. Romanelli M. Migliorini P. Evaluation of neutrophil extracellular trap deregulated formation in pyoderma gangrenosum. Exp. Dermatol. 2021; 30: 1340-1344 Crossref PubMed Scopus (4) Google Scholar ; Eid et al., 2021 Eid E. Safi R. El Hasbani G. Aftimos V. Abbas O. Kibbi A.-G. et al. Characterizing the presence of neutrophil extracellular traps in neutrophilic dermatoses. Exp. Dermatol. 2021; Crossref PubMed Scopus (5) Google Scholar ). To date, it is largely unknown which molecular events contribute to NETosis in PG.