RESUMO
Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder in humans and mice. The pearl (pe) mouse, a mouse model for the human HPS-2, bears a mutation in Ap3b1 gene. Here we investigated the pigmentation in eyes of pearl (pe) mice, and compared it with our previously published data in pale ear (ep) mice. We revealed that the hypopigmentation in eyes of pearl mice was more severe than pale ear mice, especially in the neural crest-derived tissues. However, the total tyrosinase activity in eyes of pearl mice was stronger than pale ear mice, suggesting that the degradation of aberrantly transported tyrosinase in eyes of pearl mice was weaker than that of pale ear mice. Furthermore, the pigmentation in eyes of mice doubly heterozygous for Hps1 and Ap3b1 genes was similar to the wild-type, while the hypopigmentation in iris of double mutant mice was more severe than either single mutant. Besides, we found several previously reported characters in pale ear mice, including macromelanosomes in the neural crest-derived melanocytes and increased accumulation of lipofuscin in the RPE, were absent in pearl mice. Our study indicates that Ap3b1 gene play distinct roles in melanin production and tyrosinase distribution compared with Hps1 gene.
Assuntos
Complexo 3 de Proteínas Adaptadoras/genética , Subunidades beta do Complexo de Proteínas Adaptadoras/genética , Segmento Anterior do Olho/metabolismo , Regulação da Expressão Gênica/fisiologia , Hipopigmentação/metabolismo , Melanossomas/metabolismo , Proteínas de Membrana/genética , Monofenol Mono-Oxigenase/metabolismo , Animais , Western Blotting , Modelos Animais de Doenças , Cor de Olho , Síndrome de Hermanski-Pudlak/genética , Síndrome de Hermanski-Pudlak/metabolismo , Humanos , Lipofuscina/metabolismo , Melaninas/metabolismo , Melanócitos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Pigmentação da PeleRESUMO
BACKGROUND: Hypopigmentation in hypopigmented mycosis fungoides (MF) is thought to result from the action of CD8+ cells on melanocytes. Here, we investigated the immunophenotype and melanocytic markers in hypopigmented MF lesions. METHODS: Specimens of hypopigmented lesions and normal skin from 18 patients with hypopigmented MF and specimens of non-hypopigmented lesions from 8 patients with classic/conventional MF were subjected to neoplastic immunophenotyping and melanocyte immunostaining with Melan-A, tyrosinase, stem cell factor receptor (CD117) and microphthalmia-associated transcription factor (MiTF). RESULTS: The CD8+ immunophenotype was more common in hypopigmented MF lesions (14/18) than in conventional MF lesions (1/8, p = 0.0033). There was a main effect of specimen type (hypopigmented MF lesion, hypopigmented MF normal skin, conventional MF lesion) on the number of melanocytes stained with Melan-A (median number/mm basal membrane, 1.97 vs. 4.77 vs. 5.42, respectively, p = 0.0046), tyrosinase (2.19 vs. 4.02 vs. 5.26, p = 0.0114), CD117 (4.29 vs. 7.81 vs. 5.45, p = 0.0064), and MiTF (2.75 vs. 4.43 vs. 4.98, p = 0.005). CONCLUSIONS: These results confirm previous findings of fewer melanocytes and CD117-positive melanocytes in hypopigmented MF and showed reduced MiTF identification, which is crucial for the function and survival of melanocytes. Thus cytotoxic CD8+ cell action may determine CD117/MiTF dysfunction, causing hypopigmentation.
Assuntos
Hipopigmentação , Melanócitos/patologia , Micose Fungoide , Neoplasias Cutâneas , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Hipopigmentação/metabolismo , Hipopigmentação/patologia , Masculino , Pessoa de Meia-Idade , Micose Fungoide/metabolismo , Micose Fungoide/patologia , Estudos Retrospectivos , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologiaRESUMO
BACKGROUND: Depigmented lesions (DL) have been described in areas previously damaged by inflammation in lupus erythematosus (LE). In the absence of typical lesions, distinction with other achromic diseases might be challenging. We studied the histological features and the behavior of melanocytes in these lesions. METHODS: Tissue sections of 12 patients with lupus and DL were stained with hematoxylin-eosin, periodic acid-Schiff and Fontana-Masson. Melanocytes were counted by immunohistochemistry methods using Melan A and HMB-45. Ten biopsies of normal skin were used as controls. RESULTS: The most common histological findings were: cellular infiltration (75%); hyperkeratosis (66.7%); thickening of basement membrane (66.7%); thinning and flattening of the epidermis (58.3%) and degenerative changes in collagen fibers (50%). Epidermal melanin and melanocytes were found in 41.7%. The melanocyte counts by HMB-45 and Melan A were significantly lower than in normal skin. CONCLUSIONS: The DL still fulfill histological criteria for lupus. In the absence of a precise histological diagnosis, thickening of basement membrane, hyperkeratosis, cellular infiltration, epidermal atrophy and elastosis are the most common features. Loss of melanocytes and the dermal fibrosis suggests that DL in cutaneous LE behave as post-inflammatory scars.