Immunomodulatory role of reactive oxygen species and nitrogen species during T cell-driven neutrophil-enriched acute and chronic cutaneous delayed-type hypersensitivity reactions

Rationale: Reactive oxygen species (ROS) and reactive nitrogen (RNS) are important regulators of inflammation. The exact impact ROS/RNS on cutaneous delayed-type hypersensitivity reaction (DTHR) is controversial. aim our study was to identify the dominant sources during acute chronic trinitrochlorobenzene (TNCB)-induced DTHR in mice with differently impaired production. Methods: TNCB-sensitized wild-type, NADPH oxidase 2 (NOX2)- deficient (gp91phox-/-), myeloperoxidase-deficient (MPO-/-), inducible nitric oxide synthase-deficient (iNOS-/-) were challenged TNCB right ear once elicit repetitively up five times induce DTHR. We measured swelling responses noninvasively assessed production vivo by employing chemiluminescence optical imaging (OI) probe L-012. Additionally, we conducted extensive ex analyses inflamed ears focusing biochemical morphological consequences. Results: L-012 OI revealed completely abrogated gp91phox-/- mice, 90 % decreased MPO-/- unaffected iNOS-/- mice. DHR flow cytometry analysis leukocytes derived from confirmed results. Nevertheless, observed no significant differences among all experimental groups. histopathological DTHRs slightly enhanced In contrast, a moderately reduced inflammatory immune response DTHR, while exhibited strongest Analyses lipid peroxidation, 8-hydroxy-2'deoxyguanosine levels, redox related metabolites genomic expression antioxidant proteins similar oxidative stress Furthermore, wild-type displayed neutrophil extracellular trap (NET) formation exclusively but not Conclusions: MPO NOX2 depletion one primary source only marginal conflicting Thus, single entity, each has different properties at certain stages disease, resulting outcomes.