Published online before print March 16, 2007

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1206729

Received for publication December 13, 2006.
Revised January 19, 2007.
Accepted for publication February 20, 2007.

Article

Deficient inflammatory response to UV radiation in neonatal mice

Agnieszka Wolnicka-Glubisz ^*, Jesse Damsker , Stephanie Constant , Stephanie Corn , Edward De Fabo ^*, and Frances Noonan ^*@

*Laboratory of Photobiology and Photoimmunology, Department of Environmental and Occupational Health, School of Public Health and Health Services, and Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, the George Washington University Medical Center, Washington, DC, USA; and Mouse Phenotyping Shared Resource, Department of Veterinary Biosciences, Ohio State University, Columbus, Ohio, USA

^@ To whom correspondence should be addressed. E-mail: drmfpn{at}gwumc.edu.

Abstract

Mechanisms of juvenile susceptibility to cancer are not well understood. The immune response in neonates favors nonresponsiveness or T_H2-dominant responses, raising the question of a role for neonatal immunity in this susceptibility. We have investigated the postulate that the inflammatory response differs in neonatal and adult skin. We found no inflammatory infiltrate into neonatal mouse skin in response to UV irradiation as a function of time, dose, or wavelength, although UV-induced DNA damage was readily detected. In contrast, UV irradiation of adult mice initiated a dose- and time-dependent influx of inflammatory cells, chiefly CD11b⁺Ly6G⁺ neutrophils, into the skin, detected by immunohistochemistry and quantitated by FACS analysis. This inflammatory response was initiated by UVB (290-320 nm) but not by UVA (320-400 nm). Further, in neonates, in contrast to adults, neither topical trinitrochlorobenzene (TNCB) nor i.p. thioglycollate initiated an inflammatory infiltrate. Conversely, topical TNCB applied to neonates was tolerogenic, resulting in a subsequent antigen-specific decrease of the contact-hypersensitivity response in adults. Neonatal blood contained abundant neutrophils, which exhibited impaired chemotaxis to the chemokine growth-related oncogene- but efficient chemotaxis to the bacterial product fMLP, concomitant with decreased expression of CXCR2 but normal levels of CD11b. We propose this neonatal deficiency in the inflammatory response is a significant, previously unrecognized factor in neonatal-immune tolerance and may contribute to neonatal susceptibility to cancer, including melanoma and other UV-induced cancers.

Key Words: ultraviolet • inflammation • neutrophil • contact hypersensitivity

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