Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Preferential adherence of T lymphocytes and neutrophils to psoriatic epidermis. 135 9

Adhesion receptors on endothelial cells are considered to be important for cellular influx in tissue. In this regard, skin constitutes a specialised environment for migration of leukocytes during inflammation. Using immuno-enzymatic staining techniques, we compared the in situ expression of ICAM-1, E-selectin, and VCAM-1 on endothelial cells and inflammatory infiltrates in both lesional and non-lesional biopsied skin from two immuno-inflammatory diseases, viz. psoriasis and contact dermatitis. The results were compared with those in skin specimens obtained from normal healthy individuals free from any history of skin disease. Our results show that ICAM-1 and ELAM-1 are upregulated in psoriatic non-lesional and lesional skin. On the other hand, in non-lesional biopsy from contact dermatitis patients, all three AR molecules are sparsely present, similar to the situation in normal skin although they are overtly expressed in the lesional sites. Moreover, VCAM-1 was found to be significantly increased on endothelial cells in the lesional sites of contact dermatitis as compared with biopsied psoriatic specimens. Interestingly VCAM-1 was also found to be present on some T-cells and Langerhans cells in contact dermatitis alone. The present data suggest that in different inflammatory dermatitis, varying adhesion receptor-ligand interactions involving endothelial cells and leukocytes are involved, which may be due to the differing cytokine profiles of perivascularly located T-cells.
 ...
PMID:Differential expression of ICAM-1, E-selectin and VCAM-1 by endothelial cells in psoriasis and contact dermatitis. 752 Nov 4

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.
 ...
PMID:Increased expression of adhesion receptors in both lesional and non-lesional psoriatic skin. 752 4

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.
 ...
PMID:Immunolocalization of adhesion molecules in psoriatic arthritis, psoriatic and normal skin. 753 76

As in other organs, leukocyte adhesion molecules and their ligands play a major role in cutaneous inflammatory events both by directing leukocyte trafficking and by their effects on antigen presentation. Skin biopsies of inflamed skin from patients with diseases such as as psoriasis or atopic dermatitis reveal up-regulation of endothelial cell expression of P- and E-selectin, vascular cell adhesion molecule 1 and intercellular adhesion molecule 1. Studies of evolving lesions following UVB irradiation, Mantoux reaction or application of contact allergen, demonstrate that expression of these adhesion molecules parallels leukocyte infiltration into skin. When cutaneous inflammation is widespread (e.g. in erythroderma), soluble forms of these molecules are detectable in serum. In vitro studies predict that peptide mediators are important regulatory factors for endothelial adhesion molecules. Intradermal injection of the cytokines interleukin 1, tumour necrosis factor alpha and interferon gamma into normal human skin leads to induction of endothelial adhesion molecules with concomitant infiltration of leukocytes. In addition, neuropeptides rapidly induce P-selectin translocation to the cell membrane and expression of E-selectin. Adhesion molecules also play a crucial role as accessory molecules in the presentation of antigen to T lymphocytes by Langerhans' cells. Expression of selectin ligands by Langerhans' cells is up-regulated by various inflammatory stimuli, suggesting that adhesion molecules may be important in Langerhans' cell migration. The skin, because of its accessibility, is an ideal organ in which to study expression of adhesion molecules and their relationship to inflammatory events. Inflammatory skin diseases are common and inhibition of lymphocyte accumulation in skin is likely to prove of great therapeutic benefit.
 ...
PMID:Adhesion molecules in cutaneous inflammation. 758 40

Inflammatory disorders such as autoimmune diseases and graft rejection are mediated by activated leukocytes, particularly T lymphocytes, which penetrate the inflamed tissue and perpetuate or amplify the immune reaction. In an unstimulated state, leukocytes do not readily adhere to the vascular endothelium. However, inflammatory signals induce the expression of proteins on the endothelial cell surface that promote the adhesion and extravasation of activated immune cells from the circulation into the underlying tissues. Key among these molecules are P- and E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on the endothelial cells, and their respective counter receptors, P-selectin glycoprotein ligand-1 (PSGL-1), leukocyte function-associated antigen-1 (LFA-1) and very late antigen-4 (VLA-4), on the leukocytes. In vitro blockade of these molecules inhibits the adhesion of leukocytes. In many cases there is attenuation of leukocyte activation as well. Adhesion blockade in animal models prevents or ameliorates graft rejection and disease severity in autoimmune models. Clinical studies with humanised monoclonal antibodies which interfere with LFA-1/ICAM-1 or VLA-4/VCAM-1 interactions have shown significant efficacy and good safety profiles in autoimmune disease, including psoriasis, multiple sclerosis and inflammatory bowel disease. Thus, adhesion blockade is emerging as a useful therapeutic strategy in several inflammatory settings.
 ...
PMID:Adhesion molecules as therapeutic targets for autoimmune diseases and transplant rejection. 1271 33

Inflammatory responses in all tissue compartments require the emigration of leukocytes from the microvasculature through endothelial cells into the respective microenvironment. Adhesion to endothelial cells is the most crucial step in order to facilitate selective and effective capture of leukocytes. The sequence of adhesions events, e.g. rolling, tethering, and firm adhesion are tightly regulated by a variety of molecules expressed by endothelial cells and leukocytes either constitutively or after induction by mainly inflammatory mediators. In diseases with a prominent inflammatory response such as psoriasis, rheumatoid arthritis, or Crohn's disease, interference with leukocyte adhesion and/or emigration may be of substantial clinical effect. A number of therapeutic approaches by using monoclonal antibodies, designed molecules, and other modulators of adhesion molecule expression have been investigated in clinical trials. This review aims to give an overview about the current knowledge of targeting adhesion molecules as a therapeutic strategy to treat inflammatory diseases.
 ...
PMID:Leukocyte adhesion: a suitable target for anti-inflammatory drugs. 1691 13

Efalizumab (Raptiva, Serono) is a humanised monoclonal antibody (IgG1) produced by biotechnology. This antibody has a novel place among biotherapies for psoriasis. It is bound to the CD11a subunit of a surface molecule of the T lymphocyte LFA-1 (Leucocyte Function-associated Antigen-1). This molecule is essential for binding of T lymphocytes to the ICAM-1 molecule (Intercellular Adhesion Molecule-1) found on antigen-presenting cells, endothelial cells and keratinocytes. Binding of efalizumab to CD11a prevents binding of LFA-1 to ICAM-1, thus inhibiting several steps in the immunological process responsible for formation of psoriatic plaque (activation of naive T lymphocytes to memory T lymphocytes, lymphocyte migration and reactivation of T lymphocytes in skin). Efalizumab was approved in the United States by the FDA (Food and Drug Administration) in 2003 for the treatment of moderate-to-severe psoriasis requiring systemic therapy. It may be used as first-line therapy in the United States in this indication. In France, marketing authorisation (MA) was granted more recently in September 2005. The indications are moderate-to-severe cutaneous plaque psoriasis in adults in cases of failure, intolerance or contraindication of at least two systemic treatments including phototherapy, methotrexate and cyclosporine. Current clinical trial data is available for 3500 patients with plaque psoriasis. A 75% improvement in PASI score was seen in between 22 and 39% of patients treated with efalizumab (vs. 2 to 5% for patients on placebo) in a single weekly subcutaneous injection (1 mg/kg). A study in good responders confirms the continuing long-term efficacy of prescription of the drug up to 36 months (with at least a 75% improvement in PASI score in 53% of patients). However, it is not effective against joint involvement in psoriasis. The most common side-effects (incidence >1/100) are influenza-like syndrome, risk of outbreak of cutaneous psoriasis during or after discontinuation of treatment, worsening of arthralgia, minor hypersensitivity reactions, reversible changes in laboratory values (hyperlymphocytosis, elevated alkaline phosphatases and transaminases). Because of rare cases of thrombocytopenia (incidence<1/100), reversible on discontinuation of treatment, monthly monitoring of platelet counts is required over the first 3 months of therapy. There are currently no randomised studies comparing the various systemic treatments (standard therapy and biotherapy) for psoriasis. However, on extrapolation of the available results concerning efficacy (PASI-75 after 12 weeks of treatment), efalizumab appears to be less efficacious than anti-TNF alpha agents. This drug constitutes an additional treatment option and its position in the therapeutic arsenal will depend upon its long-term benefit/risk ratio in relation to other biotherapies.
 ...
PMID:[Efalizumab]. 1705 36

Cell Communication and Adhesion has been fortunate to enlist two pioneers of epidermal and cardiac cell junctions, Kathleen Green and Mario Delmar, as Guest Editors of a two part series on junctional targets of skin and heart disease. Part 2 of this series begins with an overview from Dipal Patel and Kathy Green comparing epidermal desmosomes to cardiac area composita junctions, and surveying the pathogenic mechanisms resulting from mutations in their components in heart disease. This is followed by a review from David Kelsell on the role of desmosomal mutation in inherited syndromes involving skin fragility. Agnieszka Kobeliak discusses how structural deficits in the epidermal barrier intersect with the NFkB signaling pathway to induce inflammatory diseases such as psoriasis and atopic dermatitis. Farah Sheikh reviews the specialized junctional components in cardiomyocytes of the cardiac conduction system and Robert Gourdie discusses how molecular complexes between sodium channels and gap junction proteins within the perijunctional microdomains within the intercalated disc facilitate conduction. Glenn Radice evaluates the role of N-cadherin in heart. Andre Kleber and Chris Chen explore new approaches to study junctional mechanotransduction in vitro with a focus on the effects of connexin ablation and the role of cadherins, respectively. To complement this series of reviews, we have interviewed Werner Franke, whose systematic documentation the tissue-specific complexity of desmosome composition and pioneering discovery of the cardiac area composita junction greatly facilitated elucidation of the role of desmosomal components in the pathophysiology of human heart disease.
 ...
PMID:Highlighting Kathleen Green and Mario Delmar, guest editors of special issue (part 2): junctional targets of skin and heart disease. 2485 68