Earlier onset of neutrophil-mediated inflammation in the ultraviolet-exposed skin of mice deficient in myeloperoxidase and NADPH oxidase

Objective and design: This study examined the role of neutrophil-derived reactive oxygen species (ROS) in neutrophil recruitment into ultraviolet B (UVB)-exposed skin of mice. Methods: Mouse dorsal skin was irradiated with UVB (600mJ/cm(2)). Accumulation of neutrophils within the inflammatory sites was observed histochemically. Keratinocyte-derived chemokine (KC) and macrophage inflammatory protein 2 (MIP-2) were quantified, and in vivo chemotaxis of neutrophils toward KC and MIP-2 was examined. Results: UVB exposure of mice deficient in myeloperoxidase (MPO), NADPH oxidase, or both, caused skin neutrophil infiltration peaking at 60, 48, and 48 h, respectively, which was earlier than the 72-h peak in wild-type mice. MIP-2 level was higher in mutant than wild-type mice. Mutant neutrophils produced more MIP-2 in vitro. Neutrophil migration toward a localized source of KC was higher in mutant than wildtype mice. NADPH oxidase deficiency had a greater effect on migration than MPO deficiency. Conclusions: These results suggest that ROS produced by neutrophils regulate expression of MIP-2 and migration of neutrophils toward KC. This may explain the earlier infiltration of mutant neutrophils in response to UVB.