Deficient inflammatory response to UV radiation in neonatal mice.
Mechanisms of juvenile susceptibility to cancer are not well understood. The immune response in neonates favors nonresponsiveness or T(H)2-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-alpha 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.
Wolnicka-Glubisz
Agnieszka
A
Laboratory of Photobiology and Photoimmunology, Department of Environmental and Occupational Health, School of Public Health and Health Services, George Washington University Medical Center, Ross Hall, 2300 Eye Street, N.W., Washington, DC 20037, USA.
Damsker
Jesse
J
Constant
Stephanie
S
Corn
Stephanie
S
De Fabo
Edward
E
Noonan
Frances
F
D000818:Animals; D000831:Animals, Newborn; D000950:Antigens, Ly / Q000378:metabolism; D039481:CD11b Antigen / Q000276:immunology; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000276:immunology; D002634:Chemotaxis, Leukocyte; D004249:DNA Damage; D003872:Dermatitis / Q000276:immunology*; D007108:Immune Tolerance; D051379:Mice; D008822:Mice, Transgenic; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000276:immunology; D010853:Picryl Chloride / Q000633:toxicity; D023063:Receptors, Interleukin-8B / Q000378:metabolism; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000528:radiation effects*; D013864:Thioglycolates / Q000633:toxicity; D014466:Ultraviolet Rays / Q000009:adverse effects*
D000950:Antigens, Ly; D039481:CD11b Antigen; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; C475895:Cxcl1 protein, mouse; C480309:Ly6G antigen, mouse; D023063:Receptors, Interleukin-8B; D013864:Thioglycolates; D009240:N-Formylmethionine Leucyl-Phenylalanine; D010853:Picryl Chloride