Cells In Psoriatic Skin Research Articles

Epidermal T lymphocytes and HLA-DR expression in psoriasis.

Double staining immunofluorescent techniques and monoclonal antibodies were used to study the numbers, distribution, HLA-DR expression and relationship of T-cell subpopulations and dendritic cells in psoriatic skin. In the dermis there was a definite increase in both T helper and T suppressor cells in uninvolved skin of psoriatic patients, and the appearance of clinical lesions was not associated with any detectable change in the numbers of these cells in the dermis. In contrast, eruption of skin lesions was associated with an increase in the numbers of epidermal HLA-DR+ dendritic cells and also with epidermal influx and activation of T helper cells, while resolution of lesions coincided with increased epidermal entry and activation of T suppressor cells. Both the T helper and T suppressor cells were preferentially found adjacent to epidermal dendritic cells. These findings suggest that the clinical activity of psoriasis may be dependent upon the interaction of T helper and suppressor cells with antigen-presenting cells in the epidermis.

In situ demonstration of CD40- and CD154-positive cells in psoriatic lesions and keratinocyte production of chemokines by CD40 ligation in vitro.

In psoriatic lesions, T cells and keratinocytes are in an activated state. Ligation of CD40 expressed on activated keratinocytes with CD154 expressed on activated T cells is thought to be involved in the pathogenesis of psoriasis. However, the presence of CD40(+) and CD154(+) cells in psoriatic skin has not been thoroughly studied. The present study has therefore examined their presence by immunohistochemistry in the lesional and non-lesional skin of ten patients. The influence of CD154-CD40 ligation on the release of chemokines (IL-8, RANTES, and MCP-1) and complement components (C3 and factor B) from keratinocytes was also investigated in vitro. Studies using single and double staining showed that clusters of CD40(+) keratinocytes were present in both lesional and non-lesional skin; CD40(+)CD1a(+) Langerhans cells in lesional, non-lesional, and normal skin; and numerous CD40(+)CD83(+) cells in lesional skin. CD1a(+) and CD83(+) cells always expressed CD40 strongly. Numerous T cells were seen in lesional skin. A small number of T cells expressed CD154. CD154(+) T cells were seen in the lesional epidermis of seven of ten patients-in six, in juxtaposition to CD40(+) cells including keratinocytes. In non-lesional epidermis, CD154(+) T cells were seen in two patients-in one, in juxtaposition to CD40(+) keratinocytes. In vitro studies showed that IFN-gamma-treated keratinocytes released small amounts of IL-8, RANTES, and MCP-1; ligation of these cells with CD154-transfected J558 cells or soluble CD154 greatly enhanced the release. This ligation did not enhance the release of C3 and factor B. These results warrant further studies on the role of CD40 ligation in the pathogenesis of psoriasis.

Psoriasin (S100A7) Expression and Invasive Breast Cancer

Alteration of psoriasin (S100A7) expression has previously been identified in association with the transition from preinvasive to invasive breast cancer. In this study we have examined persistence of psoriasin mRNA and protein expression in relation to prognostic factors in a cohort of 57 invasive breast tumors, comprising 34 invasive ductal carcinomas and 23 other invasive tumor types (lobular, mucinous, medullary, tubular). We first developed an IgY polyclonal chicken antibody and confirmed specificity for psoriasin by Western blot in transfected cells and tumors. The protein was localized by immunohistochemistry predominantly to epithelial cells, with both nuclear and cytoplasmic staining, as well as occasional stromal cells in psoriatic skin and breast tumors; however, in situ hybridization showed that psoriasin mRNA expression was restricted to epithelial cells. In breast tumors, higher levels of psoriasin measured by reverse transcriptase-polymerase chain reaction and Western blot (93% concordance) were significantly associated with estrogen and progesterone receptor-negative status (P < 0.0001, P = 0.0003), and with nodal metastasis in invasive ductal tumors (P = 0. 035), but not with tumor type or grade. Psoriasin expression also correlated with inflammatory infiltrates (all tumors excluding medullary, P = 0.0022). These results suggest that psoriasin may be a marker of aggressive behavior in invasive tumors and are consistent with a function as a chemotactic factor.

Mast cells in psoriatic skin are strongly positive for interferon-gamma.

The increased number and early activation of cutaneous mast cells is a typical feature of psoriatic inflammation. Interferon-gamma (IFN-gamma) is believed to be one of the important mediators in the cytokine cascade of psoriasis. Human mast cells have been previously reported to release various cytokines upon stimulation including interleukin (IL) -4, IL-5, IL-6, IL-8, IL-13 and tumour necrosis factor-alpha. Here we report that human mast cells synthesize also IFN-gamma at mRNA and protein level and that the number of IFN-gamma producing mast cells is significantly increased in the psoriatic skin. IFN-gamma immunoreactivity in mast cells was demonstrated by staining non-lesional and lesional skin sections from 21 patients with psoriasis. Ten patients with atopic dermatitis (AD) and five healthy persons served as control groups. The percentage (mean +/- SD) of IFN-gamma + mast cells in lesional compared with non-lesional psoriatic skin was 67 +/- 18% vs. 44 +/- 17% (P < 0.0001, paired t-test), respectively, but only 9 +/- 6% vs. 10 +/- 7% in corresponding skin samples of AD. In the skin of healthy controls, only 12 +/- 12% of the mast cells were IFN-gamma +. Using immunoelectron microscopy, we confirmed the ultrastructural localization of IFN-gamma within the granules of mast cells in psoriatic skin. In addition, stimulation of a human mast cell line HMC-1 with phorbol myristate acetate (PMA) (100 nmol/L) for periods of 2-24 h induced expression of IFN-gamma mRNA, which peaked at 24 h. When HMC-1 cells were stimulated with PMA (100 nmol/L) for periods of 0-3 days, the cells released IFN-gamma protein, peaking on day 1. These results provide further evidence for the important role of mast cells in the pathogenesis of psoriasis.

Somatostatin immunoreactive dendritic cells in psoriatic skin

Somatostatin immunoreactive dendritic cells in psoriatic skin

Expression of the cutaneous lymphocyte antigen and its counter-receptor E-selectin in the skin and joints of patients with psoriatic arthritis.

We have investigated whether the skin-homing T lymphocytes identified by the cutaneous lymphocyte antigen (CLA) are increased in the synovial membrane of patients with psoriatic arthritis. Twenty-six synovial samples (13 psoriatic arthritis, seven rheumatoid arthritis, six osteoarthritis) were obtained from involved knees. Lesional skin biopsies were taken from nine of the patients with psoriatic arthritis and six patients with psoriasis alone. All samples were single- and dual-stained for CLA and CD3 (to identify T lymphocytes) using HECA-452 (anti-CLA) and anti-CD3 monoclonal antibodies. E-selectin expression was also determined. The percentage of dual-stained lymphocytes was significantly greater in psoriatic skin than in synovium (P < 0.001) and similar between psoriatic and rheumatoid synovium. There was no significant difference in the percentages of CLA-positive cells in psoriatic skin in patients with psoriatic arthritis compared with psoriasis alone. The intensity of endothelial E-selectin expression was significantly greater in skin psoriasis than in synovium (P < 2 x 10(-5)), and rheumatoid synovium had significantly greater expression than psoriatic synovium (P < 0.05). However, there was no significant correlation between E-selectin expression and the percentages of CLA-positive lymphocytes. This study provides further evidence that the CLA antigen is enriched on skin-homing lymphocytes. Conversely, the link between skin and joint inflammation in psoriatic arthritis does not seem to be explained by increased trafficking of CLA T cells to psoriatic synovium.

Inhibition of proliferation of psoriatic and healthy fibroblasts in cell culture by selected Dead-sea salts.

The effect of five selected minerals abundant in the Dead-sea brine was studied on proliferation of fibroblasts grown from psoriatic and healthy skin biopsy specimens in cell culture. The reason for carrying out this study was looking for the mechanism of the antiproliferative effect of selective Dead-sea minerals in improving the psoriatic condition. Psoriatic skin shave biopsy specimens (both from involved and uninvolved areas of the body) as well as healthy skin (obtained from amputated limbs) were incubated in tissue culture, and their outgrowing fibroblasts were used for this study. The number of cells and their cyclic AMP content were used as parameters for cell division and for proving the selective involvement of magnesium salts in the antiproliferative effect. It is shown that the inhibitory effects of magnesium bromide and magnesium chloride on cell growth were significantly stronger than those of their corresponding potassium salts or of sodium chloride. These results were obtained with both psoriatic and healthy skin fibroblasts, indicating that the inhibitory effect of the selected Dead-sea minerals is present in healthy and psoriatic skin cells.

Endothelial cell adhesion molecules in psoriasis.

Skin biopsies from patients with psoriasis and normal controls were examined for the expression of cell adhesion molecules including intercellular adhesion molecule-1 (ICAM-1), endothelial leukocyte adhesion molecule-1 (ELAM-1), HECA-452 and 4D10, using an immunoperoxidase techique. This study demonstrates that psoriatic skin exhibits a wide variety of markers of endothelial cell activation which are either induced or increased in expression (ICAM-1, ELAM-1 & 4D10). Moreover, ICAM-1 & HECA-452 are also expressed on leukocytes. These antigens may facilitate the adhesion of inflammatory cells to endothelium and antigen-presenting cells in psoriatic skin. Thus, they may play a role in faciliating the infiltration of leukocytes into psoriatic skin.

Overexpression of extracellular matrix receptors (VLA-3, 5 and 6) on psoriatic keratinocytes.

The potential role of adhesion molecules in the pathophysiology of psoriasis was investigated and the pattern of expression of the cell-surface receptors ICAM-1, LFA-3, and VLA-1, 2, 3, 4, 5 and 6 was determined in biopsies of skin from patients with psoriasis (n = 12) and from normal skin (n = 12). There were no differences in the intensity or localization of the adhesion molecules VLA-1, 2 and 4 and LFA-3. In contrast, VLA-3 and VLA-6, which are restricted to the basal keratinocytes in normal skin, were overexpressed in the spinous cells in psoriatic skin. ICAM-1 and VLA-5, which are not expressed by keratinocytes in normal skin, were focally induced, especially in cells above elongated rete ridges and where there was an infiltrate with intraepidermal granulocytes and lymphocytes.

Effects of amiprilose hydrochloride on the components of human skin equivalents

Amiprilose hydrochloride has been shown to inhibit the proliferation of a number of hyperproliferative cell types including psoriatic skin cells. In the present study, the effects of amiprilose hydrochloride on human tissue equivalents were examined by incubating a) dermal equivalents, b) skin equivalents in the process of epidermalization, and c) mature skin equivalents, with varying concentrations of the drug. In all three models amiprilose hydrochloride concentrations of 0.1% (wt/vol) and lower were not toxic to fibroblasts and keratinocytes and did not interfere with the differentiation of the skin equivalent and the developing skin equivalent. When tested in dermal equivalents, concentrations of amiprilose hydrochloride between 0.1 and 0.5% resulted in changes in fibroblast morphology with development of large intracellular vacuoles, and concentrations greater than 5% were toxic. In mature skin equivalents, in addition to changes in fibroblast morphology, amiprilose hydrochloride in concentrations of 1 to 10% affected the epidermis. When 0.5% amiprilose hydrochloride was present in the developing skin equivalent during differentiation, the epidermal keratinocytes were also affected. Thus the morphology of basal keratinocytes was modified, the differentiation was incomplete, and the dermal-epidermal attachment was compromised. These studies suggest the possibility of an extracellular mechanism of action of amiprilose hydrochloride and delineate acceptable dosage ranges for the potential drug.

Quantitative enzyme-histochemical analysis of tryptase- and chymase-containing mast cells in psoriatic skin

Tryptase-containing mast cells have recently been found to be increased in the upper dermis of psoriatic lesions. In the present study, the distribution of chymase- and tryptase-containing mast cells was morphometrically analysed at different dermal levels of lesional and non-lesional psoriatic skin (12 patients) as well as normal human skin. Mast cell tryptase was identified enzyme-histochemically, using Z-Gly-Pro-Arg-MNA as the substrate. For demonstrating mast cell chymase, a simple and specific enzyme-histochemical staining method was developed, using Suc-Val-Pro-Phe-MNA as the substrate. All mast cells positive for chymase were also positive for tryptase and Giemsa stain. Although the number of tryptase-positive mast cells was slightly increased throughout the dermis of lesional psoriatic skin, this increase was most pronounced in the upper dermis immediately beneath, and in close contact with, the epidermis. In contrast, the number of chymase-positive mast cells was clearly decreased in the upper dermis of psoriatic lesions, but not in the deeper dermis, as compared with non-lesional psoriatic skin. In addition, all chymase-positive mast cells observed in the upper dermis were very weakly stained when compared with those in the deeper dermis. No differences were found between non-lesional psoriatic skin and normal skin in which the number of mast cells containing chymase was 72-73% of the number containing tryptase. The present results suggest that T mast cells particularly, containing tryptase but no chymase, proliferate in psoriatic lesions, and that the increase in tryptase activity and the decrease in chymase activity in the upper dermis may lead to an imbalance in the biochemical regulatory systems.

Interleukin 2, soluble interleukin 2 receptor, and interferon-? in the suction blister fluids from psoriatic skin

Psoriasis represents inflammatory skin disorders characterized by significant changes in cellular immunity, particularly exhibiting alterations in T lymphocyte-related functions. Early psoriatic lesions have been reported to show an infiltration of activated helper T cells. Elevated levels of interleukin 2 (IL-2), IL-2 receptor (IL-2R), and interferon-gamma (INF-gamma) are associated with an early activation of T cells. To examine local activation of T cells in psoriatic skin, the amounts of activated T cell products, IL-2, secretory form of IL-2R (sIL-2R) and INF-gamma were measured in the fluids of suction blisters raised on psoriatic skin. sIL-2R levels were significantly elevated in the suction blister fluids raised on psoriatic involved skin compared with those on normal and psoriatic uninvolved skin. On the other hand, neither IL-2 or IFN-gamma was detected in the suction blister fluids either from normal, psoriatic uninvolved, or involved skin. However, we could detect IFN-gamma and IL-2 in the psoriatic scale extracts. Although we failed to detect IL-2 and IFN-gamma in the suction blister fluids, the increased levels of sIL-2R in the suction blister fluids from the psoriatic lesional skin indicate local activation of T cells in psoriatic lesional skin.

Rabbit antibodies against the major internal protein of a retrovirus-like particle bind to epidermal cells in psoriatic skin. Brief report.

A rabbit antiserum against the major internal protein, p27, of a psoriasis associated retrovirus-like particle has been used in indirect fluorescence microscopy of biopsies from psoriatic skin. The analysis indicate expression of p27 antigen in epithelial cells in psoriatic lesions and in clinically uninvolved psoriatic skin. A reaction of the antiserum with dermal vessel walls in the lesion was also observed.