Vitronectin in normal human skin and in skin lesions]

Vitronectin (S-protein of complement, serum spreading factor) is a multifunctional glycoprotein present in human plasma and in the elastic tissue of various organs. It belongs to the group of adhesion proteins and is of importance in the terminal stages of both the coagulation and complement system and in fibrinolysis. In human skin it is localized on dermal elastic fibers and on pathologically altered elastic material (solar elastosis, pseudoxanthoma elasticum) as well as on keratin filament material such as keratin bodies in lichen planus or amyloid deposits in localized cutaneous amyloid. It is also found in the abnormally thickened cutaneous blood vessels in erythropoietic protoporphyria and porphyria cutanea tarda. Late-stage inhibition of the complement cascade in bullous disorders in which activation of the complement system is of pathogenetic significance may be an additional important function of vitronectin in skin diseases.     

Localization of haptoglobin in normal human skin and some skin diseases

BACKGROUND: Haptoglobin (Hp) is an acute-phase reactant, known to be produced mainly in the liver. Haptoglobin can also be detected in the cytoplasm of normal epidermal Langerhans cells (LCs), and can prevent their functional maturation. The synthesis of Hp in skin cells has not been well studied. METHODS: We examined Hp expression at mRNA and protein levels by in situ hybridization and immunohistochemistry, respectively, in normal human skin and in the skin of patients with psoriasis, lichen planus, erythroderma, seborrheic keratosis, verruca vulgaris, basal cell carcinoma, systemic lupus erythematosus, pemphigus and bullous pemphigoid. RESULTS: (1) Haptoglobin mRNA was expressed in the epidermal keratinocytes (KCs), the epithelial cells of hair follicles, sebaceous glands and eccrine glands in normal skin and all dermatoses investigated. (2) Whereas compared with normal skin, the Hp mRNA in KCs of patients with psoriasis, lichen planus, erythroderma, seborrhoea keratosis and verruca vulgaris was significantly intensified, it was weaker in patients with systemic lupus erythematosus, pemphigus and bullous pemphigoid. (3) Haptoglobin protein only stained positively in some KCs of patients with psoriasis, lichen planus and erythroderma. (4) Although some but not all epidermal LCs were positively stained with anti-Hp antibody in normal skin and in skin samples from all patients, the ratios of Hp-positive LCs/total LCs were significantly higher in those diseases with intensified Hp mRNA in KCs. CONCLUSIONS: Skin is another extrahepatic organ where Hp can be synthesized by KCs. The expression of Hp mRNA in KCs and the Hp protein in both LCs and KCs appears to be correlated with the amount of inflammation, which might indicate that skin itself is involved in down-regulating the local inflammatory reaction by KC-synthesized Hp.     

Water, salts and skin barrier of normal skin

Background: We recently reported that open application of seawater for 20 min ameliorated experimental irritant contact dermatitis induced by sodium lauryl sulphate (SLS) cumulative irritation. The efficacy was overall contributed by 500 mm of sodium chloride (NaCI) and 10 mm of potassium chloride (KCl), which are consistent with the each concentration in seawater. Although the usefulness of mineral water with 500 mm NaCl and 10 mm KCl to treat atopic dermatitis (AD) or irritated skin was considered, seawater or its components would induce a feel of stinging in patients with AD. Furthermore, 20 min application was thought to be too long to use everyday as a treatment. Objective: We report the effects of 3 types of mineral water with NaCl and KCl to check the further efficacy with lesser stinging by 2 min application. Results: A mineral water with 250 mm NaCl and 50 mm KCl was the most effective water to prevent disruption of skin barrier and stratum corneum water content after cumulating irritation by SLS. Moreover, improvement of skin dryness and pruritus were shown 2 weeks after the application of the mineral water to a 6‐year‐old boy with atopic dermatitis. Conclusion: Our results suggested the possible usefulness of the mineral water with 250 mm NaCl and 50 mm KCl as the therapy of atopic dermatitis of other chronic dermatitis. Although the mineral water would not cure those skin diseases, it could be an adjunctive therapy. Further controlled clinical trials with evaluation by TEWL and capacitance are required to declare the efficacy of the mineral water in the treatment of patients with AD or other chronic dermatitis.     

Lymphocyte chemoattractants in psoriasis and normal skin

The local production of lymphocyte attractants may influence both physiologic lymphocyte trafficking in the skin as well as the infiltration of these cells in pathologic states. Recent evidence for the production of acidic lipid lymphocyte chemoattractants, particularly 12[R]-hydroxyeicosatetraenoic acid, in psoriatic lesions is reviewed. Water extractable lymphocyte attractant activity may also be recovered from both normal skin samples and psoriatic lesional stratum corneum, and may be important in the pathophysiology of lymphocyte trafficking. Less than 10 kD activity from normal skin has undergone the most detailed characterization. This has led to the isolation of a novel, as yet unidentified compound from normal skin, which we have termed "plasma-associated lymphocyte chemoattractant" (PALC).     

Amyloid P components in normal human skin and skin with lesions

Amyloid P component (AP) is a glycoprotein which is found in tissue deposits of all types of amyloid and is identical to and derived from serum amyloid P component (SAP). SAP binds in a calcium-dependent fashion to various ligands, such as agarose, desoxyribonucleic acid, fibronectin, C4-binding protein, glycosaminoglycans and isolated amyloid fibrils. Tissue AP (TAP) is also a constituent of the normal human renal glomerular basement membrane and is, in adult humans, invariably associated with elastic fiber microfibrils in connective tissue throughout the body, including that of blood vessels. In normal human skin anti-AP antibody binding was localized to the microfibrils of oxytalan fibers in the papillary dermis and to the peripheral microfibrillar mantle of elaunin and mature elastic fibers in the reticular dermis. Since SAP binds to fibronectin and glycosaminoglycans, which in turn bind to collagen fibers, TAP on elastic fiber microfibrils may play an important role in the maintenance of the normal dermal architecture and in dermo-epidermal adhesion. Under pathological conditions, AP is found in all forms of cutaneous amyloidosis, including primary localized cutaneous amyloid (PLCA); it is also detectable on keratin bodies, which represent precursor structures for PLCA. The association of AP with elastic fiber microfibrils and amyloid fibrils and their close anatomical relationship in vivo may reflect the significance of AP in the deposition of cutaneous amyloid.     

Immunolocalization of aquaporin-5 in normal human skin and hypohidrotic skin diseases

Aquaporin (AQP)‐5 has been shown to be expressed in the secretory parts of mouse, rat and horse sweat glands. However, the precise localization of AQP‐5 in normal and diseased human skin has not been fully determined. The aim of the present study was to further clarify the immunolocalization of AQP‐5 in normal human skin and hypohidrotic skin diseases. Normal human scalp skin and biopsies from skin affected by hypohidrotic diseases were analyzed for AQP‐5 and/or dermcidin expression by immunohistochemistry, immunofluorescence and/or immunoelectronmicroscopy. AQP‐5 was expressed on the apical and basolateral plasma membranes of the clear cells in eccrine sweat coils, but not in ductal components or apocrine glands. Numbers of AQP‐5‐positive coils in the secretory part of eccrine sweat glands were decreased in Sjögren’s syndrome, but not in skin affected by idiopathic segmental anhidrosis or idiopathic pure sudomotor failure. AQP‐5 was mostly localized to the plasma membranes of clear cells in the secretory coils of eccrine sweat glands, suggesting that it plays a role in producing the primary sweat fluid.     

Comparison of bacterial microbiota in skin biopsies from normal and psoriatic skin

Microorganisms have been implicated in the pathogenesis of psoriasis. Previous studies of psoriasis and normal skin have used swabs from the surface rather than skin biopsies. In this study, biopsies were taken from 10 patients with psoriasis and 12 control subjects from unmatched sites. Samples were analysed with massive parallel pyrosequencing on the 454 platform targeting the 16S rRNA gene and the variable regions V3–V4. The samples grouped into 19 phyla, 265 taxon and 652 operational units (OTUs) at 97% identity. A cut-off abundance level was set at 1%. The three most common phyla in both normal and psoriasis skin were Firmicutes (39% psoriasis, 43% normal skin), Proteobacteria (38% psoriasis, 27% normal skin) and Actinobacteria (5% psoriasis, 16% normal skin, p = 0.034). In trunk skin, Proteobacteria were present at significantly higher levels in psoriasis compared to controls (52 vs. 32%, p = 0.0113). The commonest genera were Streptococci in both psoriasis (32%) and normal skin (26%). Staphylococci were less common in psoriasis (5%) than in controls (16%), as were Propionibacteria (psoriasis 0.0001669%, controls 0.0254%). Both Staphylococci and Propionibacteria were significantly lower in psoriasis versus control limb skin (p = 0.051, 0.046, respectively). This study has shown some differences in microbiota between psoriasis and normal skin. Whether these are of primary aetiological significance, or secondary to the altered skin of psoriasis remains to be determined.     

Expression of transferrin receptor in normal human skin, psoriatic skin and various skin tumors

The distribution of transferrin receptor in normal human skin and its expression in psoriatic skin and various skin tumors have been investigated. Immuno-peroxidase staining was performed on biopsy specimens using monoclonal OKT 9 antibody, which reacts with transferrin receptor. Normal human skin showed positive staining with OKT 9 in eccrine glands and outer root sheaths of the hair. Sebaceous glands were also strongly positive. The basal layer stained very weakly. Psoriatic skin expressed OKT 9 strongly in the epidermis, especially in the area of the rete ridge. In squamous cell carcinoma, Bowen's disease, and malignant melanoma, a widespread and strong labelling reaction was found. Basal cell epithelioma and genital Paget's disease were partially and moderately positive in their staining pattern. No such positive staining pattern could be found in either nevus cell nevi or seborrhoic keratosis. These findings indicate that, in normal skin, transferrin receptor exists in eccrine glands, sebaceous glands, and outer root sheaths of the hair in greater amounts. High amounts of expression of this receptor in psoriatic epidermis and malignant tumors suggests that immunohistochemical demonstration of transferrin receptor parallels the proliferating activity of the tissue or tumor of the skin and may provide an useful aid for detecting such conditions.     

Expression of BMI-1 in normal skin and inflammatory and neoplastic skin lesions

BACKGROUND: BMI-1 is involved in the maintenance of stem cells and functions as an oncogene in both lymphomas and solid carcinomas, acting by downregulation of p16ink4a. We have investigated the expression profile of BMI-1 in normal and inflamed skin as well as in basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs). METHODS: BMI-1 expression was determined by immunohistochemistry and immunofluorescence, and evaluated semiquantitatively. RESULTS: BMI-1 was weakly expressed in nuclei of basal and sometimes suprabasal keratinocytes, in basal cells of sebaceous glands, weakly to moderately in the bulge area and the external root sheath of hair follicles, and strongly in sweat glands. Whereas BCCs showed strong and diffuse BMI-1 expression, SCCs expressed BMI-1 heterogeneously. Strong cytoplasmic expression of BMI-1 was found in dividing cells. CONCLUSIONS: BMI-1 expression marks stem cells within the hair follicle. As BMI-1 was also found in suprabasal keratinocytes and a variety of specialized cells, the distribution of BMI-1 only partly reflects the known distribution of stem cell compartments. BMI-1 is strongly overexpressed in BCCs, tumors linked to dysregulation of the sonic hedgehog pathway, which has been shown to upregulate BMI-1, suggesting a contribution of the BMI-1 oncogene in their pathogenesis.     

Differential expression of cornified cell envelope precursors in normal skin,intraorally transplanted skin and normal oral mucosa

BACKGROUND: Skin flaps have routinely been used as substitutes for oral mucosa after extensive resection of oral tissues. However, it remains unknown how the transplanted skin flaps perform as a host defence in the new environment of the oral cavity. OBJECTIVES: To evaluate the expression of cornified cell envelope (CCE) precursors in pretransplanted (normal) skin, intraorally transplanted skin and normal oral mucosa, because CCEs are highly responsible for a protective barrier in each type of epithelium. METHODS: We used immunohistochemistry and immunoelectron microscopy to examine the expression of CCE precursors, small proline-rich protein (SPR) 2 and 3 and loricrin, in biopsy specimens of normal skin, transplanted skin and normal oral mucosa, including buccal and lingual (non-keratinized) mucosae, and palatal (keratinized) mucosa. RESULTS: Transplanted skin flaps were classified into two groups. About two-thirds of the transplanted skin flaps displayed a reddish appearance and were devoid of the stratum corneum (SC) together with a psoriasiform inflammatory tissue reaction. Others showed a native appearance, retaining the SC. While SPR2 expression was limited to the stratum granulosum (SG) in both normal and transplanted skin retaining the SC, it extended to the stratum spinosum (SS) of the transplanted skin lacking the SC and that of the normal oral mucosa. Although SPR3 expression was not found in normal skin or in the transplanted skin retaining the SC, it was strongly expressed in the SS of the transplanted skin lacking the SC and the non-keratinized oral mucosa, and in the SS and SG of the keratinized oral mucosa. Loricrin, which was expressed in the SG of normal skin, the transplanted skin retaining the SC and the keratinized oral mucosa, was not detected in the transplanted skin lacking the SC or in the non-keratinized oral mucosa. Immunoelectron microscopy confirmed the ultrastructural localization of SPR3 directly under the cytoplasmic membrane of keratinocytes of the transplanted skin lacking the SC and that of the oral mucosa. CONCLUSIONS: The altered expression of SPR2, SPR3 and loricrin reflects the possible adaptation of epidermal keratinocytes in the new environment of the oral cavity.     

CD44 expression in normal and inflamed skin

CD44 is the principal cell surface receptor for hyaluronate. In non-inflamed skin, CD44 expression is limited to the cell membrane of eccrine coil cells. The distribution on these cells is assymetric, with intense staining on the dermal side and little staining on the luminal side of the coil cell. In skin containing a pathologic process, either inflammatory or neoplastic, CD44 expression can be widespread on the membranes of keratinocytes and on infiltrating lymphocytes in the vicinity of the process. Diverse roles have been proposed for CD44 and largely involve aspects of cellular adhesion in one setting or another. CD44 may identify a more mobile, proliferating keratinocyte that is responding to local injury. In eccrine coil, the stable presence of CD44 on the non-luminal surface of secretory cells indicates an undefined function for CD44 in the generation of eccrine sweat.