title: Differential effects of ultraviolet irradiation in neonatal versus adult mice are not explained by defective macrophage or neutrophil infiltration.
abstract: Epidemiological studies suggest that ultraviolet B exposure (UVR) during childhood is the most important environmental risk factor for melanoma. In accordance, neonatal, but not adult, UVR exacerbates melanoma incidence in mouse models. The inability of neonates, as opposed to adults, to mount a proper neutrophil inflammatory response in the skin upon UVR exposure has been one of the driving hypotheses explaining this observation for the past decade. However, this aspect remains controversial. Here, we evaluated the UVR-induced inflammatory response in neonatal versus adult mice. In neonates, a significant neutrophil infiltration could be identified and quantified using three different antibodies by flow cytometry or immunohistochemistry. On day 1 after UVR, neutrophils were increased by 84-fold and on day 4 macrophages increased by 37-fold compared with nonexposed age-matched skin. When compared with adults, neonatal skin harbored a higher proportion of neutrophils in the myeloid compartment without significant differences in absolute counts. This response was reproduced with different kinetics in C57Bl/6 and FVB mice with a more rapid attenuation of neutrophil counts in the latter. Overall, our results suggest that the greatly increased sensitivity to melanomagenesis in neonates does not result from their incompetence in terms of myeloid inflammatory response to UVR.
authors: University of Queensland Centre for Clinical Research, Brisbane, Queensland, Australia.
authors: Mathieu P
authors: MP
authors: Rodero
authors: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors: Herlina Y
authors: HY
authors: Handoko
authors: The University of Queensland, UQ Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia.
authors: Rehan M
authors: RM
authors: Villani
authors: QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
authors: Graeme J
authors: GJ
authors: Walker
authors: University of Queensland Centre for Clinical Research, Brisbane, Queensland, Australia; The University of Queensland, UQ Diamantina Institute, Translational Research Institute, Brisbane, Queensland, Australia. Electronic address: k.khosrotehrani@uq.edu.au.
authors: Kiarash
authors: K
authors: Khosrotehrani
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D049109:Cell Proliferation / Q000528:radiation effects; D005434:Flow Cytometry; D008264:Macrophages / Q000473:pathology* / Q000528:radiation effects; D008545:Melanoma / Q000453:epidemiology / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000473:pathology / Q000528:radiation effects; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology / Q000276:immunology / Q000473:pathology*; D009504:Neutrophils / Q000473:pathology* / Q000528:radiation effects; D012307:Risk Factors; D012878:Skin Neoplasms / Q000453:epidemiology / Q000276:immunology / Q000473:pathology*; D014466:Ultraviolet Rays / Q000009:adverse effects*