银屑病患者血清和皮损中血管内皮细胞粘附分子的对比研究

目的 探讨银屑病患者血清和皮损中4种血管内皮粘附分子表达与银屑病疾病活动性之间的关系。方法 采用ELISA法检测36例银屑病患者治疗前后和36例健康人的血清中可溶性粘附分子（sICAM-1、sICAM-3、sVCAM-1、sELAM）的浓度。同时用ABC免疫组化染色技术检测了36例银屑病患者皮损和临床治愈处皮肤粘附分子（ICAM－1、ICAM－3、VCAM－1、ELAM）的表达情况。结果 与正常人相比，银屑病患者皮损部位4种粘附分子的原位表达呈明显上调（P＜0.005），同时患者血清中4种可溶性粘附分子浓度也明显升高（P＜0.001）。经治疗后银屑病患者皮损部位4种粘附分子的原位表达明显下调（P＜0.05），同时血清中4种可溶性粘附分子浓度比前也下降（P＜0.05）；血清中4种可溶性粘附分子的浓度与银屑病疾病活动严重指数（PASI）均呈正相关，但治疗前后sVCAM-1的水平上升和下降的幅度最大，且与PASI的相关性最好。结论 血管内皮细胞粘附分子参与银屑病的发病机制；患者血清中可溶性粘附分子浓度的升高可能与皮损部位血管内皮细胞上相应的粘附分子高表达有关；血清VCAM－1的水平可以作为反映银屑病疾病活动的一个新的敏感指标。     

Preferential adherence of T lymphocytes and neutrophils to psoriatic epidermis

T lymphocytes and neutrophils accumulate in psoriatic epidermis. To determine whether the epidermis plays an active role in this process through the production of cellular adhesion factors, leucocyte adherence to lesional psoriasis was compared with normal skin in a modified frozen-section adhesion assay. Lymphocyte and neutrophil suspensions were prepared by standard Ficoll-Hypaque techniques from peripheral blood of normal volunteers and overlaid on to glutaraldehyde-fixed 8-microns cryostat sections of skin. Adhesion of phorbol ester-activated T lymphocytes to the epidermis was significantly greater in psoriasis compared with normal skin (P < 0.01). Adhesion was absent (a) at 7 degrees C, (b) in the presence of EDTA and (c) in the absence of lymphocyte activation. Immunostaining demonstrated that all adherent lymphocytes were CD3+ve (i.e. T cells). Likewise, neutrophils adhered more prominently to psoriatic epidermis. Adhesion was most prominent at the tips of dermal papillae, corresponding to areas of maximal intercellular adhesion molecule-1 (ICAM-1) expression. Both neutrophils and lymphocytes adhered to dermal papillary vascular endothelium. These studies provide functional data that psoriatic epidermal cells are actively involved in leucocyte adherence. The distribution of adhesion suggests that both ICAM-1-dependent and independent mechanisms are involved.     

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 expression (ICAM-1, ELAM-1 & 4D10). Moreover, ICAM-1 & HECA-452 are also 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.     

Immunolocalization of adhesion molecules in psoriatic arthritis, psoriatic and normal skin

Adhesion molecule expression in synovial membrane obtained from patients with psoriatic arthritis (PA) has previously been compared with rheumatoid arthritis (RA). Although expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was similar in both psoriatic and rheumatoid synovium, in contrast, little or no endothelial leucocyte adhesion molecule-1 (ELAM-1) was observed in psoriatic synovium. In the present study, the expression of ICAM-1. ELAM-1 and VCAM-1 was examined in the involved and uninvolved skin from patients with PA (n= 15), patients with psoriasis (Ps) but no arthritis (n= 5) and in normal skin (n= 4). ICAM-1 was intensely expressed on endothelium and keratinocytes of involved skin from patients with Ps with or without arthritis. There was constitutive expression of ICAM-1 on endothelium only in uninvolved and normal skin. In contrast, ELAM-1 expression was restricted to endothelial cells; it was widespread and intense in involved skin, but was minimal in uninvolved and normal skin. VCAM-1 was expressed on endothelium, and also on some dendritic cells in involved psoriatic skin. There was minimal VCAM-1 staining on endothelial cells in uninvolved and normal skin. In conclusion, in involved psoriatic skin from patients with and without arthritis ICAM-1, ELAM-1 and VCAM-1 expression is up-regulated on vascular endothelium, and ICAM-1 is expressed on keratinocytes. However, ELAM-1 and VCAM-1 expression seen in dermal vessels is not found in psoriatic synovial vessels. These differences suggest a mechanism for controlling cellular traffic in Ps and in PA.     

Adhesion of peripheral blood mononuclear cells and CD4+ T cells from patients with psoriasis to cultured endothelial cells via the interaction between lymphocyte function-associated antigen type 1 and intercellular adhesion molecule 1

BACKGROUND: The adhesion of CD4+ T cells to endothelial cells and their subsequent migration to skin tissue are essential to develop the psoriatic skin lesion. However, few studies have examined the role of adhesion molecules in the binding of T cells from patients with chronic plaque psoriasis to endothelial cells in vitro; thus, the adhesion molecules responsible for the development of skin lesions are still unclear. OBJECTIVES: To identify the responsible adhesion molecules in the interaction between CD4+ T cells in patients with chronic plaque psoriasis and cytokine-stimulated endothelial cells. METHODS: An in vitro adhesion assay between Calcein-labelled peripheral blood mononuclear cells (PBMC) and cytokine-stimulated human endothelial cultures, which exhibit a higher adhesion capacity to PBMC, was established, and the adhesion-inhibitory effects of a panel of antiadhesion molecule antibodies on the adhesion of PBMC from patients with psoriasis to endothelial cells were examined. Then, the inhibitory effects of selected antibodies acting on the interaction between CD4+ T cells from patients with psoriasis (purified by negative magnetic cell sorting) and cultured endothelial cells were examined. RESULTS: A significant increase (P < 0.01) in the adhesion of psoriatic PBMC to both endothelial cultures, human skin microvascular endothelial cells from adults (HMVEC-Ad) and human coronary arterial endothelial cells (HCAEC), compared with healthy PBMC, was demonstrated in our in vitro cell adhesion assay. Pretreatment of both endothelial cultures with tumour necrosis factor (TNF)-alpha (1000 U mL(-1)) induced the most frequent adhesion of PBMC from patients with psoriasis among the three inflammatory cytokines examined, i.e. TNF-alpha, interleukin-1beta and interferon-gamma [TNF-alpha-treated vs. nontreated: P < 0.001 (in both HMVEC-Ad and HCAEC)]. In both endothelial cultures treated with TNF-alpha, PBMC from patients with psoriasis exhibited significantly more frequent adhesion compared with those from healthy individuals (P < 0.001). The TNF-alpha-stimulated HMVEC-Ad, which exhibited the most frequent adhesion of PBMC, were selected for adhesion-inhibition experiments using monoclonal antibodies (mAbs) to adhesion molecules that are upregulated in psoriatic lesions, and the combination of antilymphocyte function-associated antigen type 1 (LFA-1) and anti-intercellular adhesion molecule 1 (ICAM-1) mAbs gave the greatest reduction of adhesion of PBMC from patients with psoriasis (approximately 69% reduction; P < 0.01). This combination of mAbs significantly reduced also the adhesion of CD4+ T cells from patients with psoriasis to TNF-alpha-stimulated HMVEC-Ad (approximately 62% reduction), compared with pretreatment with isotype control mAbs (P < 0.01). CONCLUSIONS: These findings indicate that the LFA-1/ICAM-1 interaction plays a major role in the adhesion of CD4+ T cells to endothelial cells and that TNF-alpha might play an important role for the induction of adhesion molecules on endothelial cells at psoriatic skin lesions.     

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.     

Soluble E-selectin serum levels correlate with disease activity in psoriatic patients

E-selectin is an adhesion molecule expressed on vascular endothelial cells in several inflammatory skin diseases, including psoriasis. It is responsible for the adherence between microvascular endothelium and neutrophils, monocytes, eosinophils and subsets of T cells. Soluble E-selectin (sE-selectin) serum levels were measured by ELISA in 32 psoriatic patients before treatment and compared with both post-treatment sE-selectin levels in 16 patients and sE-selectin values in 10 healthy individuals. Soluble E-selectin serum levels were significantly increased in psoriatic patients compared with healthy persons. Moreover, a significant correlation was demonstrated between sE-selectin values and PASI scores. No relationship was found between sE-selectin levels and duration of psoriasis. Soluble E-selectin serum levels decreased significantly after treatment of psoriasis. This phenomenon was more evident in patients with more severe psoriasis. In conclusion, sE-selectin serum levels correlate with the extent of psoriatic lesions and could be used as marker of the disease activity in psoriatic patients.     

Resolution of psoriasis by a leukocyte-targeting bacterial protein in a humanized mouse model

Psoriasis is a very common chronic skin disease, affecting 2-3% of the world's population or more than 125 million individuals worldwide. The characteristic lesion of psoriasis is due to rapid proliferation and shortened transition of keratinocytes through the epidermis. Proinflammatory white blood cells (WBCs) migrate into the psoriatic plaques, and the pathogenic cytokine environment causes the changes in keratinocyte proliferation and differentiation. Enhanced migration of WBCs is due to the upregulation and activation of adhesion molecules such as leukocyte function antigen-1 (LFA-1), which binds intercellular adhesion molecule-1 (ICAM-1) on endothelial cells. Targeting LFA-1 and preventing interaction with ICAM-1 has proven an effective strategy for treating psoriasis. We show here that a natural leukocyte-targeting bacterial protein (leukotoxin (LtxA)) that binds LFA-1 can inhibit proliferation of activated WBCs from psoriasis patients and demonstrates significant therapeutic efficacy in a psoriasis xenograft transplantation model. In ex vivo studies, LtxA preferentially targeted proinflammatory WBC subtypes, including activated CD25(+) T cells and CD14(+)CD16(+) monocytes. LFA-1 has been shown to have a significant role in the pathogenesis of numerous autoimmune and inflammatory diseases, and we propose that LtxA may be a highly effective agent for treating these diseases.     

Psoriatic keratinocytes prime neutrophils for an overproduction of superoxide anions

Psoriatic plaques result from an abnormal proliferation of keratinocytes associated with the local presence of T lymphocytes and neutrophils. The exact role of neutrophils in psoriatic lesions remains unclear. The present investigation was aimed at deciphering the capacity of psoriatic keratinocytes to alter in vitro functions of neutrophils. Blood neutrophils from healthy donors were incubated with psoriatic (PK) or healthy keratinocytes (HK) with and without IL-2-activated healthy T lymphocytes. The study was focussed on neutrophil capacity of adherence, viability and superoxide anion production. PK or HK with or without T lymphocytes similarly augmented neutrophil viability after 48 h of co-incubation. PK or HK did not directly activate the superoxide production by neutrophils. However, they both primed neutrophils for an increased fMLF-induced production of superoxide, an effect enhanced by the presence of T lymphocytes. PK were 1.5-fold more efficient than HK to augment this superoxide production. PK cultured with T lymphocytes induced the adhesion of neutrophils 4.7 times more efficiently than HK. The adherence of neutrophils was mediated through ICAM-1, LFA-1 and Mac-1, independently of bioactive lipids. The effects of PK and HK on neutrophil viability and priming were independent of direct cellular contact. In conclusion, keratinocytes can impact neutrophils by increasing their lifespan, and by priming them to overproduce superoxide. PK are more efficient than HK in priming neutrophils, an effect enhanced by T lymphocytes. These results indicate that neutrophils could contribute to psoriasis pathogenesis partly through their pathological interactions with PK.     

The role of the immune system in the pathogenesis of psoriasis

Psoriatic involved skin contains an increased number of activated T cells. The mechanism through which these T cells achieve and maintain their activated state is unknown, and both antigen-dependent and -independent mechanisms may contribute. Recently a novel pathway of antigen-independent T-cell activation has been described. This pathway is identified by a monoclonal antibody that binds to a T-cell membrane surface molecule termed "UM4D4.". This molecule is expressed on a minority (20%) of psoriatic peripheral blood T cells but on a majority (75%) of the T cells in lesional skin. Thus, UM4D4 could play a role in antigen-independent T-cell activation in psoriasis. Indeed the monoclonal antibody anti-UM4D4 consistently induces proliferation of psoriatic UM4D4+ T-cell clones. The activity of antigen-dependent pathways are also enhanced in psoriatic epidermis in as much as involved skin relative to uninvolved skin contains an increased number and function of antigen-presenting cells. Upon activation, the lesional T cells release lymphokines. Central to the immune hypothesis of psoriasis is that some of these T-cell lymphokines act on keratinocytes to induce changes characteristic of psoriasis. Indeed lymphokines from lesional psoriatic T-cell clones directly alter in vitro keratinocyte phenotype through induction of intercellular adhesion molecule-1 (ICAM-1) and HLA-DR cell-surface expression. Furthermore, the lymphokines also enhance keratinocyte growth. These data suggest a critical role for the immune system in the pathogenesis of psoriasis.     

Serum level of sELAM-1 in psoriatic patients correlates with disease activity

BACKGROUND: Endothelial leucocyte adhesion molecule-1 (ELAM-1) acts as an adhesion ligand for neutrophils and monocytes and the expression of this molecule on the vascular endothelium may reflect its ability to recruit neutrophils from circulation. The next step is the transendothelial migration of neutrophils into lesional psoriatic skin. ELAM-1 may also exist in a soluble form. METHODS: We determined the serum levels of ELAM-1 by ELISA in 41 patients with psoriasis and 20 controls. RESULTS: Patients with acute psoriasis displayed higher levels of ELAM-1 (85.45 +/- 47.72 ng/ml) than controls (36.02 +/- 15.60 ng/ml) and patients with chronic disease (61.24 +/- 27.91 ng/ml). In 25 patients we measured the serum level of ELAM-1 twice: at the beginning and after treatment of the disease and we did not find any significant changes. We also found a correlation between serum ELAM-1 and PASI score. CONCLUSIONS: These data suggest that there is a high serum level of E-selectin in psoriatic subjects even after clearing of the disease. Serum E-selectin may reflect the general activation of endothelial cells in the disease and may be a new sensitive marker of disease activity.     

Mast cells of psoriatic and atopic dermatitis skin are positive for TNF-α and their degranulation is associated with expression of ICAM-1 in the epidermis

Abstract The release of cytokines from cutaneous cells may be of major importance in the initiation and development of many inflammatory skin disorders. For example, tumor necrosis factor-alpha (TNF-α), which in healthy skin is found preformed only in mast cells, is able to induce the expression of several adhesion molecules including intercellular adhesion molecule-1 (ICAM-1). Increased expression of ICAM-1 occurs in keratinocytes in lesional skin of psoriasis and atopic dermatitis (AD) and it is considered to be an important initiator of leucocyte/keratinocyte interactions in skin inflammation. We counted the mast cells showing TNF-α immunoreactivity using a double-staining method in nonlesional and lesional skin sections from 12 patients with AD and 12 patients with psoriasis. The percentage of TNF-α⁺ mast cells in lesional and nonlesional AD skin was 36 ± 22% and 21 ± 15% (P < 0.018, paired t-test), respectively, and in psoriatic skin was 16 ± 25% and 15 ± 15%, respectively (P < 0.89, paired t-test). We also cultured whole skin biopsies taken from the healthy-looking skin of psoriatic and AD patients in the presence of mast cell degranulator compound 48/80, which resulted in focal expression of ICAM-1 in the epidermis. In cultured keratinocytes, both histamine and an extract of a human mast-cell line (HMC-1) induced ICAM-1 immunostaining only in occasional cells, but the combination of histamine and the HMC-1 extract resulted in intense ICAM-1 staining in numerous cells. This enhancement of ICAM-1 staining was abolished by preincubation of the HMC-1 extract with anti-TNF-α antibody. These results suggest that the degranulation of mast cells induces the expression of ICAM-1 in keratinocytes probably via TNF-α and histamine. Received: 8 August 1997     

A ligand of human thy-1 is localized on polymorphonuclear leukocytes and monocytes and mediates the binding to activated thy-1-positive microvascular endothelial cells and fibroblasts

Thy-1 is known to be expressed on fibroblasts, nerve cells, and blood stem cells. Previous studies have shown the induction of Thy-1 on phorbol ester stimulated human dermal microvascular endothelial cells in vitro. In situ Thy-1 expression was found on activated endothelium. In this study we were interested in the localization of a Thy-1 ligand and the characterization of the function of Thy-1 on human dermal microvascular endothelial cells and fibroblasts. Human Thy-1 purified from fibroblast extracts was labeled and used as a probe for the detection of a Thy-1 ligand. In cryostat sections of bullous pemphigoid skin a Thy-1 ligand was found on inflammatory cells, whereas the Thy-1 antigen was expressed on the endothelial cells and fibroblasts. By flow cytometry we could show the expression of a Thy-1 ligand on polymorphonuclear leukocytes and monocytes, whereas lymphocytes did not express this Thy-1 ligand. To study whether Thy-1 is involved in cell-cell adhesion we separated Thy-1-positive and Thy-1-negative cells by magnetic cell separation using the monoclonal antibody AS02. Cell adhesion assays and blocking experiments revealed a direct involvement of the Thy-1/Thy-1 ligand interaction in the binding of monocytes and polymorphonuclear leukocytes to Thy-1-positive activated endothelial cells and fibroblasts.     

银屑病皮损ICAM-3表达的免疫组化研究

用卵白素生物素酶复合物法 ( ABC法 )对 2 0例银屑病患者皮损处的 ICAM- 3表达进行了免疫组化研究。结果表明 :ICAM- 3染色阳性细胞的密度在银屑病皮损部位较非皮损部位以及经局部外用皮质激素治疗后肉眼恢复正常的皮肤部位均有统计学意义的显著增高 ( P<0 .0 0 1)。结果提示银屑病皮损部位 ICAM- 3的表达异常增高可能参与银屑病的发病机制     

Overexpression of extracellular matrix receptors (VL-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.     

IL-4 expression by neutrophils in psoriasis lesional skin upon high-dose UVB exposure

BACKGROUND: Upon a single high dose of UVB irradiation of psoriatic lesional skin, IFN-gamma expression is decreased, whereas IL-4 expression is enhanced. A similar type 1 to type 2 shift was found in dermal T cells derived from irradiated lesional skin as compared to unexposed lesional psoriatic skin. We have found recently that the IL-4 protein detected in situ upon UVB exposure of normal skin was not associated with T cells but with infiltrating neutrophils. OBJECTIVE: To determine which cell types express IL-4 in psoriatic skin after UVB irradiation. METHODS: Skin biopsies were obtained from healthy controls and psoriasis patients before and after local UVB exposure. Double immunohistochemical stainings were performed to determine the identity of IL-4-expressing cells. RESULTS: In the irradiated skin of both healthy controls and patients, IL-4-positive cells coexpressed elastase and CD15, but not CD3. CONCLUSION: IL-4-expressing cells found in psoriatic skin after a single high-dose UVB exposure appeared to be neutrophils.     

Upregulation of RANTES in psoriatic keratinocytes: a possible pathogenic mechanism for psoriasis

Intraepidermal collections of neutrophils and lymphocytes are unique features of the inflammatory reaction of psoriasis. Migration of leukocytes from dermis to the epidermis suggests a role for chemotactic agent(s). In recent years, increased levels of chemokines such as IL-8 , GRO-a and MCP-1 have been reported in the keratinocytes of psoriatic tissue. IL-8 and GRO-alpha belong to a subfamily (C x C) class and MCP-1 is a beta chemokine. In this study, we investigated RANTES, which is a beta chemokine (C-C class); RANTES has been found to be associated with various cell-mediated hypersensitive disorders. We obtained eight skin biopsies from chronic psoriatic plaques, and five biopsies each from non-lesional psoriatic skin, lichen planus, eczematous dermatitis and skin from healthy controls. Snap-frozen samples were cut into 7 microm cryosections and stained with 6 mg/ml of monoclonal anti-RANTES mouse IgG (DNAX, Palo Alto, CA). Standard immunohistochemistry techniques were applied. RANTES was detected only in the keratinocytes. The number of keratinocytes in per mm2 of epidermis stained for RANTES were 116.79+/-98.42 in psoriatic tissues compared to 32.00+/-46.05 (p<0.05), 6.39+/-3.59 (p<0.01), 2.64 +/-1.15 (p<0.01) and 3.53+/-5.26 (p<0.01), respectively, in the non-lesional, lichen planus, eczematous lesions and normal skin. This is the first study to report that the keratinocytes of psoriatic tissue express high levels of RANTES compared to the controls. IL-8 and related molecules (C x C class) are predominantly chemotactic for neutrophils and MCP-1 is a strong chemotactic factor for monocytes. In contrast, RANTES is chemotactic for memory T cells and activated naive T cells. Increased amounts of RANTES as reported here provide an explanation for migration of the activated T cells to the epidermis of the psoriatic lesions. In addition, RANTES activates T cells. These results suggest that RANTES may have a significant role in the inflammatory process of psoriasis. Our findings further substantiate a regulatory role for keratinocytes in the inflammatory process of psoriasis.     

Effect of in vivo interleukin-1 on adhesion molecule expression in normal human skin.

We have examined the expression of three endothelial adhesion molecules (intercellular adhesion molecule-1 [ICAM-1], endothelial leukocyte adhesion molecule-1 [ELAM-1], and vascular cell adhesion molecule-1 [VCAM-1]) in normal human skin following intradermal injection of stratum corneum-derived interleukin-1 alpha (SCIL-1 alpha). In control skin, constitutive expression of ICAM-1 was found on endothelial cells and at low levels on dermal dendritic cells but not on keratinocytes. ELAM-1 and VCAM-1 were present in low levels on endothelium and perivascular dendritic cells, respectively. SCIL-1 alpha injection produced marked endothelial ELAM-1 upregulation. Double staining with neutrophil elastase demonstrated that many ELAM-1-positive vessels contained marginating neutrophils and that interstitial neutrophils were clustered around ELAM-1-positive vessels. An increase in dermal dendritic cell ICAM-1 expression occurred and in two of three biopsies there was keratinocyte expression of ICAM-1 in the SCIL-1 alpha-injected tissue. Also, there was upregulation of VCAM-1 on vascular endothelium and an increase in the dermal dendritic cell expression of this molecule. These results give in vivo confirmation that SCIL-1 alpha modulated endothelial and dermal dendritic cell adhesion molecule expression, and show that endothelial VCAM-1 is regulated in vivo by SCIL-1 alpha, thus providing a regulatable ICAM-1-independent means of mononuclear cell recruitment.     

Osteopontin: a new emerging role in psoriasis

Osteopontin (OPN) is a phosphorylated acidic glycoprotein produced by cells of the immune system, epithelial tissue, smooth muscle cells, osteoblasts, and tumor cells. OPN interacts with integrins and CD44 to enhance Th1 and inhibit Th2 cytokine expression. The involvement of this molecule in the onset of psoriasis has not previously been studied. Here, we demonstrate that OPN is expressed in peripheral blood mononuclear cells and in skin biopsies of psoriatic patients. The study was conducted on 30 patients affected with plaque psoriasis, and on 11 healthy donors. Two blood samples and two skin samples from patients affected with atopic dermatitis were used as control for Th2 typical inflammatory skin disease. The analysis of IL-1β, IFN-γ, ΤΝF-α, IL-8, and ICAM-1 showed the characteristic Th1 pattern in all the psoriatic blood and skin samples analyzed. This study offers an opportunity for understanding inflammation in psoriasis and supports the hypothesis that OPN could represent a potential target for therapeutic intervention in psoriatic patients.