摘要:

Immunohistochemical and immunoserological evidence supports the involvement of both cell‐mediated and humoral mechanisms in the pathogenesis of melanocyte destruction in vitiligo. Punch biopsies from depigmented vitiliginous skin (VS), normal‐looking pigmented skin (PS), and marginal skin (MS) from patients with generalized vitiligo (n = 15) were labeled with K 1.2.58, OKM1 (CD11b), Leu 11b (CD16), Leu 19 (CD56), IFN‐γreceptor, IL‐2 receptor (CD25), IgG, IgM, C3c, and C3d MoAbs. In addition, in vitro effects of vitiligo sera (n = 13) on human newborn melanocytes (HMel) under different culture conditions were studied.The immunohistochemical findings showed absence of K 1.2.58+ epidermal melanocytes in VS and abnormal morphology in MS. In these areas, a few CD11b + cells in the dermis and epidermis could be detected but no significant numbers of CD16+ or CD56+ cells were seen among the mononuclear cellular infiltrate. IL‐2 and IFN‐γ receptors were clearly expressed by the cellular infiltrate. No significant deposition of complement or immunoglobulin was seen.The addition of vitiligo sera to HMel cultures induced a significant cellular proliferation. The stimulation of cell proliferation occurred regardless whether the sera were added alone or when preheated (56°C for 1 hr) and then supplemented with a complement source (P<0.01 at 2%,P<0.001 at 10%, andP0.05 at 2%,P<0.05 at 10%, andP<0.01 at 20% for decomplemented sera plus complement). In contrast, incubation of vitiligo sera together with normal lymphocytes with HMel significantly decreased the number of living melanocytes in a dose dependent manner, suggesting an antibody‐dependent cellular cytotoxicity (ADCC) reaction (P<0.01 at 2% and 10%,P<0.001 at 20%).The presence of lymphocytic infiltrate at marginal skin with evidence for IL‐2‐ and IFN‐γ‐receptor expression and the decrease in the number of living cells by ADCC‐like mechanisms provide further support for an autoimmu

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1994.tb00013.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Previous workers have shown that mammals have tyrosinase and tyrosinase related proteins (TRPs) that share common structural domains, all of which are not present in microbial tyrosinases. We report here the deduced amino acid sequence of a TRP from fish that is highly homologous to mammalian TRP‐1. Examination of the structures of these vertebrate tyrosinases and TRPs shows that, aside from the conserved cysteine‐rich and histidine‐rich domains previously noted, there are a large number of conserved prolines and glycines, leading to an abundance of turns and few conserved helical regions. These tyrosinases and TRP‐1s also have in their cytosolic tails a consensus sequence that is not present in any other protein. It is proposed that this sequence may participate in directing these proteins to the mela

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1994.tb00014.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1994.tb00782.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

TheWlocus encodes a tyrosine kinase receptor,c‐kit, which affects survivial of melanoblasts from the neural crest. The primary cochlear defect inViable Dominant Spotting(Wv/Wv) mutants is a lack of melanocytes within the stria vascularis (SV) associated with an endocochlear potential (EP) close to zero and hearing impairment. In this study, we compare inner ear pigmentation with cochlear potentials in three otherWalleles (Wx, Wsh, andW41) and reveal an unequivocal correlation between presence of strial melanocytes and presence of an EP. Asymmetry was common, and 8.3% ofWsh/Wx, 25% ofWsh/Wsh, 60% ofW41/Wx, and 69.2% ofW41/W41ears had a pigmented stria and an EP, while the remainder had no strial melanocytes and no EP. In those mutants that partially escaped the effects of the mutation, strial melanocytes rarely extended the entire length of the stria, but were confined to the middle and/or basal turns of the cochlea. The extent of strial pigmentation was unrelated to the EP value, which was measured from the basal turn only. Compound action potential (CAP) responses recorded from ears with an EP were variable and they showed greatly raised thresholds or were absent in all ears where the EP was close to zero. In controls, melanocytes in the vestibular part of the ear were found in the utricle, crus commune, and ampullae, whereas in many mutants only one or two of these regions were pigmented. There was a broad correlation between pigmentation of the stria and pigmentation of the vestibular region but this was not absolute. AllW41/Wx,Wsh/Wsh, andW41/W41mutants had some pigment on the pinna but, in contrast to controls where melanocytes were found in the epidermis and dermis of the pinna, pigment cells were reduced in number and generally restricted to the dermis. Injection of normal neural crest cells into 9.5‐day‐old mutant embryos increased the extent of skin pigmentation on the head and coat of adult chimeras and was associated with a small increase in the proportion of pigmented s

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1994.tb00015.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

An ex vivo model system was developed to investigate melanocyte migration. Within this model system, melanocytes migrate among other epidermal cells in the epibolic outgrowth of skin explants. This process is initiated by loss of contact inhibition of epidermal cells at the rim of the explants and by locally produced chemotactic factors. Punch biopsies provided explants of reproducible diameter. Optimal culture conditions include medium consisting of Dulbecco's Minimal Essential Medium containing 10% inactivated normal human serum and placement of explants epidermal side up at the air‐liquid interphase. Within 7 days, epidermal cells completely surround the explant. Approximately 3 days after the onset of keratinocyte migration, melanocytes distribute themselves within the newly formed epidermis. Throughout the 7‐day culture period, melanocytes and keratinocytes show maintenance of subcellular morphology, and the dermo‐epidermal junction remains intact. Melanocyte migration was quantified using immunoperoxidase staining in combination with light microscopy and computer‐aided image analysis. Preliminary results using the model system to compare migration in control and nonlesional vitiligo skin indicate that no inherent migration defect is responsible for impaired repigmentation of vitiligo lesions. The organotypic culture model system allows for investigations on melanocytes within their environment of autologous epidermal and dermal components, closely resembling in vivo circumstances in hum

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1994.tb00016.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Stem cell factor (SCF) is hypothesized to play a critical role in the migration of melanocytes during embryogenesis because mutations in either the SCF gene, or its ligand, c‐kit, result in defects in coat pigmentation in mice and in skin pigmentation in humans. In this report we directly show that SCF alters the adhesion and migration of human melanocytes to extracellular matrix (ECM) ligands and regulates integrin expression at the protein level. SCF decreased adhesion of neonatal and fetal cells to collagen IV, and increased attachment of fetal cells to laminin. Attachment of fetal cells to fibronectin was decreased, but was unchanged in neonatal cells. Flow cytometry analysis of neonatal melanocytes showed that SCF down‐regulated the expression of the α2 receptor, and up‐regulated the expression of the α3, α5 and β1 integrin receptors. SCF down‐regulated expression of α2, α5 and β1 integrins by fetal melanocytes, and up‐regulated expression of the αv and α3 integrin receptors. Analysis of melanocyte migration using time‐lapse videomicroscopy showed that SCF significantly increased migration of neonatal, but not fetal, melanocytes on fibronectin (FN). We conclude that SCF regulates integrin expression at the protein level and that SCF has pleiotropic effects on melanocyte attachment and migration on ECM ligands. We suggest that this may be one mechanism by which SCF regulates melanocyte migration during dev

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1994.tb00017.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The ink sac epithelium of the cuttlefishSepia officinaliswas investigated by electron microscopy. Melanogenesis in a simplified view seems to follow the general scheme of melanin formation in vertebrates. First, a membrane‐bound protein matrix is formed, which is called an early stage melanosome. The early stage melanosomes are more or less irregular in shape with a size up to 1.5 μm and contain membranous, granular, or vesicular material. They seem to originate from Golgi bodies and/or endoplasmic reticulum. Membranes that frequently are present in the early stage melanosomes may originate from fusion of vesicles or from incorporation of Golgi membranes into early stage melanosomes. Free cytoplasmic material or mitochondria probably are also incorporated into the early stage melanosomes or melanosomes. Therefore, the origin of the early stage melanosomes seems to be similar to that of autophagosomes. The early stage melanosomes mature to melanosomes in which several dozen melanin granules are formed. These melanosomes, at last, release the melanin granules together with other cellular material, including early stage melanosomes, into the lumen of the ink gland. This finding confirms the earlier postulated holocrine character of the release. Active tyrosinase was localized in the lumen of the ink sac as already shown by biochemical methods. There was also additional evidence that most of the material of broken down cells inside the lumen of the ink sac seems to be converted into melanin granul

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1994.tb00018.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Odor perception within olfactory neuroepithelium and pigment translocation within melanophores both seem to rely on a cAMP‐based second messenger system.From studies on cultured frog melanophores, Lerner et al. (Proc. Natl. Acad. Sci. USA 85:261‐264, 1988) suggested that some aspect of odor perception may be mediated by a nonspecific mechanism whose signal is transduced by a cAMP‐based second messenger system.In the present study, odorants (β‐ionone, benzylaldehyde, cineole, cinnamaldehyde, and octanol), which previously have been shown to stimulate formation of cAMP in the olfactory neuroepithelium, were investigated for possible pigment dispersing and cAMP‐increasing effects. Pretreatment of fish melanophores with the adenylate cyclase activator forskolin (1 μM) resulted in an approximately 300% increase in cAMP and an almost complete blockage of noradrenaline‐induced pigment aggregation. However, none of the tested odorants were able to increase the cAMP level and only cinnaldehyde and β‐ionone were found to have any pigment dis

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1994.tb00019.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY