Incorporation of 14C-linoleic acid in cerebrosides of psoriatic and normal human skin

Summary Psoriasis is marked by loss of glycocalyx. Glycocalyx is composed of glycoproteins and glycolipids such as cerebrosides. It was shown that the incorporation of ¹⁴C-linoleic acid in cerebrosides of normal and psoriatic human skin is different. In psoriatic epidermis and corium the turnover of this fatty acid is significantly elevated. It is suggested that in psoriasis the epidermal cell is not able to build up a regular carbohydrate sequences of lipids because the false carbohydrate chain activates the degradation of glycolipids and in compensating for the increased degradation raises the synthese rate of glycolipids.     

Mitogenic effects of sera from normal and psoriatic subjects on human skin fibroblasts

Summary Sera from normal and psoriatic subjects had similar mitogenic effects when added to monolayer cultures of human skin fibroblasts. Fibroblasts derived from a psoriasis patient proliferated faster in both types of sera than fibroblasts from a normal subject, despite similar rates of proliferation in foetal calf serum. The psoriatic fibroblasts appeared to be inherently capable of a greater response to human serum mitogens than the normal fibroblasts.     

Immunohistochemical localization of lysyl oxidase in normal human skin

Lysyl oxidase (EC 1.4.3.13), a copper-dependent enzyme which catalyses the formation of aldehyde cross-links, and acts primarily on collagen and elastin, is known to be increased during wound healing and in fibrotic disorders including liver cirrhosis and atherosclerosis, and to be decreased in some hereditary connective tissue diseases and in malignant cell lines. A recent study showed that lysyl oxidase might possess tumour suppressor activity as an antioncogene for ras. Little is known about the localization of this enzyme in human skin. In this study, we determined immunohistochemically the localization of lysyl oxidase in normal skin of young and elderly subjects obtained from sun-exposed and unexposed regions of the body. All skin samples tested had similar distributions of lysyl oxidase. The enzyme was present both extracellularly and intracellularly. Extracellularly, a few granular aggregates of immunoreactants were observed along collagen and elastic fibres. These granules were more common in the adventitial portion of the dermis than in the reticular portion. Of all sun-exposed and unexposed regions studied, the skin of the face displayed the greatest amount of extracellular immunoreactants. Immunopositive granules were observed intracellularly in fibroblasts, vascular endothelial cells, sweat glands, sebaceous glands, arrector pili muscles and some keratinocytes. These findings provide evidence that, as suggested in recent reports, lysyl oxidase may have a variety of intracellular functions.     

Immunohistochemical localization of interleukin-6-like immunoreactivity to peripheral nerve-like structures in normal and inflamed human skin

Interleukin-6-like (IL-6-like) immunoreactivity was sought in inflamed and normal human skin using the same immunohistochemical technique as for detection of neuropeptides. Such immunoreactivity was found in dermal and in a few intraepidermal nerve-like fibres in biopsy specimens from inflamed skin from patients with positive epicutaneous patchtest reactions to nickel sulphate, and in skin specimens from patients with atopic dermatitis and prurigo nodularis. However, IL-6-like immunoreactivity was also found in nerve-like fibres in specimens from nonlesional skin. In skin from patients with positive epicutaneous patch-test reactions there was a statistically significantly (P<0.01) higher number of IL-6-positive nerve fibres in the epidermis than in normal skin, in contrast to the papillary dermis, in which no difference was found. Moreover, there were clusters of nerve-like fibres with IL-6-like immunoreactivity in the dermis of prurigo nodularis lesions. In these nerve-like fibres, the colocalization of the immunoreactivities for IL-6 and calcitonin gene-related peptide was indicated. Localization of immunoreactivity to nerve-like structures surrounding the eccrine sweat glands indicates that IL-6 is present in autonomic as well as in sensory nerve fibres.     

Increased expression of adhesion receptors in both lesional and non-lesional psoriatic skin

Adhesion receptors and their ligands play a vital role in the immune system. We studied the expression of different adhesion receptors, using single- and double-staining immunohistochemical techniques, in both lesional and non-lesional skin specimens from seven psoriasis patients and in skin biopsy specimens from eight normal healthy controls. Our results showed an overall increased expression of several adhesion receptors in both lesional and non-lesional psoriatic skin. We consistently found an increased expression in particular of ICAM-1 and E-selectin on endothelial cells, and ICAM-1 on T cells and Langerhans cells. In contrast, a weak expression of VCAM-1 was found on endothelial cells and mononuclear cells in lesional psoriatic skin specimens alone. Interestingly, LFA-1 was also expressed on Langerhans cells, with a greater frequency in skin from lesional than from non-lesional sites, but was never expressed in skin from normal healthy individuals. Furthermore, significantly increased numbers of Langerhans cells and T cells with a positive reactivity for MAb HECA-452 were found in both lesional and non-lesional psoriatic skin. We hypothesize that the enhanced expression of adhesion receptors on migrating immunocompetent cells and endothelial cells of psoriatic skin in general facilitates the increased influx of activated T lymphocytes and other immunocomponent cells into the skin, and thus underscores the generalized character of the disease.     

Immunohistochemical localization of type V collagen in normal human skin

Summary Tissue distribution of type V collagen in normal human skin was studied using an indirect immunofluorescent technique to determine whether type V collagen is present in the interstitium or in the basement membrane. Type V collagen was isolated from the human placenta by pepsin digestion and was purified with fractioning salt precipitations. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that type V collagen contained 1(V) and 2(V) chains, but not the 3(V) chain. Specificity of the rabbit antibodies to type V collagen was assessed using enzyme-linked immunosorbent assay (ELISA) and an immunoblotting method. Antibodies showed no cross-reactivity to other collagens, laminin, and fibronectin. With an indirect immunofluorescent technique, type V collagen was found to be widely distributed throughout the dermis. Intense fluorescent staining was noted in the papillary dermis and adnexal dermis surrounding hair follicles and eccrine glands. The basement membrane of the dermoepidermal junction, skin appendages, and capillaries was not stained. By indirect immunoperoxidase double staining, type V collagen was not found to be deposited on type IV collagen present in the basement membrane. Immunoelectron microscopic studies showed that type V collagen was not located in the basal lamina. These results suggest that type V collagen is distributed in the interstitium, but not in the basement membrane of normal human skin.     

Immunohistochemical localization of urokinase- and tissue-type plasminogen activators in psoriatic skin

Biopsies of involved and uninvolved skin from psoriatic patients and of normal skin were stained immunocytochemically with monoclonal antibodies against urokinase-type (u-PA) and tissue-type (t-PA) plasminogen activator using a multilayer peroxidase technique. Epidermis from psoriatic lesions showed focal staining for u-PA in and between the basal keratinocytes in the suprapapillary epidermal areas, while t-PA was found in the superficial keratinizing cells, including both stratum spinosum and the parakeratotic layer. No staining of keratinocytes was observed in uninvolved and normal skin. The specificity of the staining was supported by the finding that 3 different monoclonal antibodies and polyclonal antibodies against each of the plasminogen activators gave identical staining, while monoclonal antibodies of irrelevant specificity gave no staining. The present findings suggest abnormalities in the regulation of both types of plasminogen activators in psoriatic epidermis.     

In situ localization of interferons in psoriatic lesions

Summary An indirect immunofluorescence technique, using murine monoclonal antibodies (MoAbs) against human IFN- and human IFN- was used to study IFNs in cryostat sections from psoriatic skin lesions. The IFNs were more pronounced in sections from highly active psoriasis than in sections from stationary psoriasis. In highly active psoriatic lesions IFNs- was localized to keratinocytes in stratum basale, to some epidermal dendritic cells, probably Langerhans cells, and to some mononuclear cells in dermis. IFN- was usually not detected in sections from stationary psoriasis. IFN- was localized to stratum corneum, to keratinocytes around microabcesses and to mononuclear cells in the dermal cell infiltrates, predominantly in highly active psoriatic lesions. Both IFN- and IFN- were localized to some endothelial cells in the papillary dermis. The MoAbs did not stain sections from unaffected skin from patients with psoriasis or sections from healthy individuals. The findings indicate that the IFN system in the skin may be of significance in the pathophysiology of psoriasis.     

LTA4 hydrolase in human skin: decreased activity,but normal concentration in lesional psoriatic skin

Leukotriene A₄ (LTA₄) hydrolase which transforms LTA₄ into the proinflammatory compound LTB₄ has been identified in human epidermis. The purpose of this study was to investigate the potential role of this enzyme in psoriasis, in which LTB₄ is present in biologically active concentrations. The concentration and activity of LTA₄ hydrolase was determined in normal skin and in matched samples of involved and uninvolved psoriatic skin. The enzyme content was determined using an affinity-purified antibody. This antibody was also used for immunohistochemical staining of skin biopsies. Immunohistochemically LTA₄ hydrolase was localized predominantly in the basal and spinous layers in normal skin and in involved and uninvolved psoriatic skin. The LTA₄ hydrolase content varied between 2.8 and 3.1 μg enzyme/mg protein and was found to be similar in normal and psoriatic skin, involved as well as uninvolved. In contrast, the activity of the enzyme was decreased significantly in involved psoriatic skin (9.9±2.1 μg LTB₄/mg enzyme per min) compared with matched uninvolved psoriatic skin (16.4±3.5 μg LTB₄/mg enzyme per min), but was decreased only insignificantly compared with normal skin (12.4±1.8 μg LTB₄/mg enzyme per min). It was found that the conversion of LTA₄ to LTB₄ results in inactivation of LTA₄ hydrolase activity. This finding is compatible with the idea that the decreased LTA₄ hydrolase activity in involved psoriatic skin reflects transcellular LTB₄ formation in vivo. In peripheral lymphocytes the enzyme content was 1.3±0.3 μg enzyme/mg protein in normal lymphocytes and 1.4±0.3 μg enzyme/mg protein in psoriatic lymphocytes, which was significantly lower than in the skin. In contrast, the specific LTA₄ hydrolase activities in normal and psoriatic lymphocytes (23.4±1.3 and 21.3±1.7 μg LTB₄/mg enzyme per min) were significantly higher than in normal skin. These findings may indicate the existence of LTA₄ hydrolase isoforms in human lymphocytes and human skin.     

Thrombomodulin expression on dermal cells in normal and psoriatic skin

Abstract The various subsets of dermal cells with a dendritic appearance can be identified by phenotypic differences in cell markers. We report on the morphology and tissue distribution of dermal cells detected with a monoclonal antibody against thrombomodulin in histological sections of normal arm and scalp skin and psoriatic skin. Double staining with antibodies to factor XIIIa, CD34 and CD68 was also employed in scalp biopsies to elucidate the relationship between thrombomodulin⁺ dermal cells and dermal dendrocytes and macrophages described by others. Thrombomodulin⁺ dermal cells in normal arm skin had little cytoplasm with fine branched dendrites and tended to be localized just beneath the epidermis. In scalp skin these cells had longer, more numerous dendrites and were distributed in the papillae and perivascular adventitial dermis primarily in the upper and central reticular dermis. In psoriatic skin, thrombomodulin⁺ dermal cells had an increased cytoplasmic volume with stout, less branched dendrites and appeared in the papillae and among inflammatory cells. Dermal cells detectable by thrombomodulin expression were factor XIIIa^–, CD34^– and CD68^–, and seemed to represent a distinct subset of dermal cells which may function in tissue repair. However, thrombomodulin⁺ dermal cells and factor XIIIa⁺ dendrocytes were frequently seen close together and could act cooperatively to regulate extravascular thrombin homeostasis in both normal and pathological dermal environments. Received: 26 May 1997     

Altered cutaneous innervation in psoriatic skin as revealed by PGP 9.5 immunohistochemistry

Summary There is conflicting evidence in the literature as to whether cutaneous nerves are altered in psoriasis or not. In this study, antibodies to protein gene product (PGP) 9.5 were used to visualize cutaneous nerves in biopsies from involved and uninvolved skin of nine patients with psoriasis and from normal skin of eight healthy controls. A profound reduction in the epidermal nerve fibre density was observed in the involved psoriatic skin. These intraepidermal nerve fibres were also mostly short and found in the basal layer. Only a few nerve fibres were found in the suprabasal layer and they were non-varicose, long fibres going straight up without branching. In the uninvolved skin of psoriatic patients, the distribution and number of the intraepidermal nerve fibres was similar to that observed in normal skin. In the dermis, the distribution and the number of the nerve fibres showed no differences between involved psoriatic skin, uninvolved psoriatic skin, and normal skin. The results support previous studies in which alterations of cutaneous nerves in psoriasis have been described.     

Expression of serotonergic receptors in psoriatic skin

Psoriasis appears to be influenced by stress, which causes release of adrenal hormones. Serotonin, or hormonal actions on serotonin and serotonin receptors, may have a role in psoriasis. Distribution of serotonin receptors was studied in involved and noninvolved skin in patients with psoriasis and compared to normal skin, by using immunohistochemistry and antibodies to 5-HT1A, 5-HT2A and 5-HT3 receptors (R). There was a decreased (P<0.001) number of 5-HT1AR positive cells, the majority being tryptase positive, in involved and noninvolved psoriatic papillary dermis, compared to normal skin. 5-HTlAR expression was also found in the upper part of the epidermis, on vessel walls and on melanocytes. 5-HT2AR expressing papillary mononuclear cells, CD3 positive, were increased (P<0.001 and P<0.01, respectively) in involved and noninvolved psoriatic skin, compared to normal skin, an increase (P<0.01) also being found in the involved compared to noninvolved skin. Expression of 5-HT3R could be found in the basal epidermal layer of noninvolved but not in the involved skin of psoriasis, where it was only found in the acrosyringium. The present findings are compatible with the 5-HT1A and 5-HT2A receptors having antagonistic functions, and raise the possibility of using receptor specific drugs in the treatment of psoriasis.