Earlier onset of neutrophil-mediated inflammation in the ultraviolet-exposed skin of mice deficient in myeloperoxidase and NADPH oxidase.
OBJECTIVE
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 (600 mJ/cm2). 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 wild type 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.
Komatsu
J
J
Kihara Institute for Biological Research, Yokohama City University, Maioka-cho 641-12, Totsuka, Yokohama, 244-0813, Japan.
Koyama
H
H
Maeda
N
N
Aratani
Y
Y
D000818:Animals; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines / Q000494:pharmacology; D019743:Chemokines, CXC; D002634:Chemotaxis, Leukocyte; D003872:Dermatitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015846:Monokines / Q000494:pharmacology; D019255:NADPH Oxidases / Q000172:deficiency* / Q000235:genetics; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects*; D009195:Peroxidase / Q000172:deficiency* / Q000235:genetics; D012867:Skin / Q000276:immunology / Q000473:pathology / Q000528:radiation effects; D014466:Ultraviolet Rays
D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC; C475895:Cxcl1 protein, mouse; D015846:Monokines; C074302:keratinocyte-derived chemokines; D009195:Peroxidase; D019255:NADPH Oxidases; D020780:Matrix Metalloproteinase 9