Reduction of lymphatic vessels in photodamaged human skin

Abstract

Chronic ultraviolet B (UVB) irradiation (290-320 nm) of the skin results in the degradation of extracellular matrix macromolecules, elastosis, formation of wrinkles [1] and enhanced risk for skin cancer [2] . We have previously found that chronic UVB irradiation of human and mouse skin induces pronounced angiogenesis of cutaneous blood vessels [3;4]. Moreover, targeted overexpression of vascular endothelial growth factor (VEGF)-A enhanced the sensitivity to UVB-induced cutaneous photodamage [5], whereas transgenic overexpression of the angiogenesis inhibitor thrombospondin-1 in the epidermis completely prevented UVB-induced skin damage [3]. Together, these findings indicate that the cutaneous blood vasculature plays a critical role in the mediation of photodamage. In contrast, the role of cutaneous lymphatic vessels in the response to UVB irradiation has remained unknown.Lymphatic vessels play a crucial role in the maintenance of tissue fluid homeostasis [6], and our recent results obtained in mouse models indicate that impairment of lymphatic vessel function is involved in the mediation of acute UVB-induced skin damage in mice because of increased leakiness of lymphatic vessels that was induced by enhanced levels of VEGF-A [7;8]. To investigate the consequences of chronic UVB irradiation of human skin on cutaneous lymphatic vessels, we obtained skin samples from the face (sun-exposed skin; 2-mm punch biopsies from the crow's feet area not including wrinkles) and from the buttocks (non-sunexposed skin; 4-mm punch biopsies) of 17 healthy Korean volunteers. All procedures involving human subjects were approved by the Institutional Review Board of Seoul National University Hospital, and all subjects provided written informed consent. Facial skin samples were divided into 3 groups, according the the previously described scoring system for the severity of photodamage in Korean individuals [9]: Group 1: grades 1-3 (n=6); group 2: grades 4-5 (n=6); and group 3: grades 6-7 (n=5). Grade1 corresponds to absence of wrinkles whereas grade 7 corresponds to severely wrinkled skin [9].We performed double immunofluorescence stains for the panvascular marker CD31 (BD Biosciences, Pharmingen, San Diego, CA) and for the lymphatic-specific hyaluronan receptor LYVE-1 (kindly provided by Dr. D. Jackson, Oxford, UK) as described [10]. By Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript fluorescence microscopy, the density of LYVE-1 positive lymphatic vessels was apparently reduced in the dermis of sample...

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