j. Soc. Cosmet. Chem., 47, 117-128 (May/June 1996) Effect of chronic actinic exposure on epidermal Langerhans cells of different ethnic groups MASATO HATAO, TRACY STOUDEMAYER, J. LEON LICHTIN, ADEL SAKR, and ALBERT M. KLIGMAN, Cosmetic Sciences Program, College of Pharmacy, University of Cincinnati Medical Center, 3223 Eden Avenue, Cincinnati, OH, 45267-0004 (M.H., J.L.L., A.S.), S.K.I.N., Incorporated, 151 East Avenue, Conshohocken, PA, 19428 (T. S.), and Department of Dermatology, University of Pennsylvania, 422 Curie Boulevard, Philadelphia, PA 19104-6142 (A.M.K.). Accepted for publication September 27, I995. Presented in part at the 18th World Congress of Dermatology, New York, June 13, I992. Correspondence to Masato Hatao, Shiseido Research Center, 1050 Nippa-cho, Kohoku-ku, 223 Yokohama, Japan Synopsis Langerhans cells are epidermal dendritic cells that function as antigen-presenting cells and play a role in a total immune system. It has been reported that UVB radiation damages and decreases the number of epidermal Langerhans cells. However, baseline data from human studies with regard to chronic actinic exposure are limited. In this study, normal Caucasian and African-American volunteers of two age ranges and without recent sunlight exposure were studied, taking the dorsal forearm and the inner aspect of the upper arm as representative areas with and without chronic actinic exposure. From statistical analysis, a factor of age showed a statistically significant effect on Langerhans cell density, but chronic actinic exposure did not induce any decrease of Langerhans cell density in any of the subject groups. Although age is statistically significant, only the older African-American group showed slightly lower Langerhans cell density. These facts suggest that the Langerhans cells are replenished constantly up to 70 years of age and that their level is unaffected by chronic actinic exposure in healthy volunteers. INTRODUCTION During the past 20 years, the immune function of the skin has been undergoing detailed study following the recognition by Silberberg-Sinakin et al. of the Langerhans cell's function in processing foreign antigens for presentation to T lymphocytes (1). The acute effects of UVB exposure on Langerhans cell density are also well documented. Aberer et a/, reported that 80 mJ/cm 2 of UVB radiation on human skin produced a virtually complete elimination of Langerhans cell membrane markers 24 hours after radiation (2). Baadsgaard et al. reported that 4 MED of UV radiation reduced the percentage of T6 and HLA-DR positive cells at three days after irradiation (3). Gilchrest et al, demonstrated that 3 MED of UV radiation decreased the number of Langerhans cells 24 hours after 117

118 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS radiation (4). Alcalay et al. reported that low-dose UVB radiation (between 0.75 and 1.5 MED) decreased the number of ATPase-positive epidermal Langerhans cells to between 21% and 65% (5). In animal studies, UVB-induced reduction of Langerhans cell density was observed in a dose-dependent manner (6,7). However, UVB radiation did not decrease the number, but impaired the function of Langerhans cells in vitro (8,9). Much less is known about the effect of chronic sun exposure. Thiers et al. studied an older population with clinical evidence of sun-damaged skin and compared the skin of the arm and the buttock regions (10). They concluded that chronic sun exposure resulted in a decrease of ATPase-positive Langerhans cells. Gilchrest et al. reported that the number of Langerhans cells in sun-exposed areas was statistically significantly fewer than in paired sun-protected specimens (11). Delo et al. reported that the density of Langerhans cells in chronic actinically damaged skin at the posterior neck was significantly decreased compared to that of control skin (12). In this study, we investigated the effect of chronic actinic exposure on Langerhans cell density not in a photodamaged skin but in a normal skin, since the Langerhans cells in the photodamaged skin might be decreased by the secondary effect of the other derreal damage. Thus, the relatively limited data for normal skin and the availability of mono- clonal antibodies for more specific immunohistochemical identification of Langerhans cells prompted us to carry out this study ofdendritic cell populations in sun-exposed and sun-protected skin from young and elderly individuals of two ethnic groups. Another reason for the present study was the limited baseline data on Langerhans cells in normal human skin from individuals of different age ranges and ethnic backgrounds. Studies designed to assess age-related changes include that of Gilchrest et al. (4), who showed an age-associated decrease in the population of Langerhans cells in Caucasians by comparing four young and seven old subjects, both male and female. Thiers et al. (10) showed a significant decrease in the number of ATPase-positive Langerhans cells in skin from elderly patients when compared to that from young medical students. Gilhar et al. reported that the number of HLA-DR positive Langerhans cells in sun-protected thigh skin decreased with age (13). As for animals, a reduction of Langerhans cells in aged murine ear epidermis was reported (14), and the Langerhans cell density of C57BL/6J mice was found to decrease with age (15). With regard to ethnic background, Berman et al. found no differences between the mean densities of Langerhans cells in skin from male or female Caucasians and Hispanics (16). However, no baseline data for the Langerhans cell density in African-Americans is available at present. From the previous epidemiological study, UV-induced skin cancers are rare among African-Americans. Therefore, it is intriguing to investigate the effect of chronic sun exposure on the Langerhans cell density in African-Americans. MATERIALS AND METHODS STUDY SUBJECTS Thirty-seven female volunteers (13 Caucasians aged under 30 years, ten Caucasians aged over 60 years, seven African-Americans aged under 33 years, and seven African-Amer- icans aged over 59 years) participated in the main study. One Caucasian male volunteer with a clinically photodamaged skin also participated in the study. All subjects enrolled