NETosis in the pathogenesis of acute lung injury following cutaneous chemical burns

• DOI: 10.1172/jci.insight.147564
• Publication Date: 2021-05-23T18:01:11Z
• Authors: Ranu Surolia; Fu Jun Li; Zheng Wang; Mahendra Kashyap; Ritesh Kumar Sriv...; Amie M. Traylor; Pooja Singh; Kevin G. Dsouza; Harrison Kim; Jean-Francois Pittet; Jaroslaw W. Zmije...; Anupam Agarwal; Mohammad Athar; Aftab Ahmad; Veena B. Antony
• Keywords: Neutrophil Extracellular Traps; Pathogenesis; Barrier function

Despite the high morbidity and mortality among patients with extensive cutaneous burns in intensive care unit due to development of acute respiratory distress syndrome, effective therapeutics remain be determined. This is primarily because mechanisms leading lung injury (ALI) these unknown. We test hypothesis that chemical promote systemic activation neutrophils, particular, toxicity mediated by deployment neutrophil extracellular traps (NETs). also demonstrate potential benefit a peptidyl arginine deiminase 4 (PAD4) inhibitor prevent NETosis preserve microvascular endothelial barrier function, thus reducing severity ALI mice. Our data demonstrated phenylarsine oxide (PAO) treatment neutrophils caused increased intracellular Ca2+-associated PAD4 activity. A dermal burn lewisite or PAO resulted activation, NETosis, ALI. NETs disrupted function cells human cell spheroids. Citrullinated histone 3 alone Pharmacologic genetic abrogation inhibited following burns. Cutaneous PAD4-mediated NETosis. inhibitors may have as countermeasures suppress detrimental after