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

Adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and its counter-receptor, lymphocyte function associated antigen-1 (LFA-1), play very important roles in immune responses. In this study, the effects of cytokines on cultured human melanoma cells (MMG2) were examined, especially focussing on the expression of ICAM-1 on MMG2 and lymphocyte adhesion to MMG2. Both the expression of ICAM-1 and HLA-DR on MMG2 increased after treatment with IFN-gamma. ICAM-1 expression began to increase earlier than HLA-DR expression. TNF-alpha and IL-1 beta also increased the expression of ICAM-1 on MMG2. However, these cytokines did not increase the expression of HLA-DR. IFN-gamma had a dose dependent effect on lymphocyte adhesion to MMG2. Pretreatment of IFN-gamma treated MMG2 with 84H10 (anti-ICAM-1 antibody) or pretreatment of lymphocytes with either SPV-L7 (anti-LFA-1 alpha antibody) or IOT10 (anti-LFA-1 beta antibody) inhibited the lymphocyte adhesion to MMG2. These results suggest that ICAM-1 molecules induced on melanoma cells by IFN-gamma can interact with LFA-1 molecules on lymphocytes.
J Dermatol 1993 Mar
PMID:Intercellular adhesion molecule-1 on cultured human melanoma cells: influence of cytokines. 809 20

The pathogenetic mechanisms involved in the development of drug-induced erythema multiforme (EM) are still largely unknown. The observation that epidermal keratinocytes (KC) in EM express intercellular adhesion molecule-1 (ICAM-1) points to a putative role for T-cell/KC adhesion in the pathogenesis of EM. In this study, the binding of peripheral blood mononuclear leucocytes (PBML) from a patient with carbamazepine-induced EM and of normal control PBML to autologous and heterologous KC was investigated, using two different binding assays. Patient PBML obtained at the time of disease (t0) showed an increased binding to ICAM-1-positive heterologous KC, which could be inhibited completely by anti-LFA-1. Adhesion of patient PBML-t0 to autologous KC, and to carbamazepine-pretreated heterologous KC in sections of skin biopsies, was also increased, but was found to be only partially LFA-1-dependent. These findings support the view that PBML/KC adherence plays an important role in the pathogenesis of this drug-induced EM.
Br J Dermatol 1993 Jul
PMID:Increased adherence to keratinocytes of peripheral blood mononuclear leucocytes of a patient with drug-induced erythema multiforme. 836 10

Fibroblasts interact with the extracellular matrix through cell-surface receptors belonging to the integrin family. In this report, we present evidence that cultured normal human fibroblasts express the integrin alpha 4 beta 1 and that this receptor facilitates fibroblast attachment to fibronectin. Fluorescence-activated cell sorter analysis and immunoprecipitation with monoclonal antibodies demonstrated that normal dermal fibroblasts express the alpha 4-subunit on the cell surface, primarily in association with the beta 1-subunit. Cell-attachment assays demonstrated that normal human fibroblasts can attach to the 40-kDa fibronectin fragment containing the type III connecting segment domain recognized by alpha 4 beta 1. Adhesion to this fragment was inhibited by anti-alpha 4 antibody. Furthermore, our results indicate that alpha 4 beta 1 collaborates with another fibronectin receptor, alpha 5 beta 1, during fibroblast attachment to full-length fibronectin. The region of fibronectin recognized by alpha 5 beta 1 contains the amino acid sequence arg-gly-asp (RGD). A short synthetic RGD peptide, or the 120-kDa fibronectin fragment containing the RGD sequence, only partially inhibited attachment to full-length fibronectin, suggesting that fibroblasts utilize more than the RGD recognition sequence for binding to fibronectin. Accordingly, RGD peptide combined with anti-alpha 4 antibody produced more potent inhibition of cell attachment than either reagent alone. These observations show for the first time that functional alpha 4 beta 1 fibronectin receptor is not restricted to lymphoid cells and transformed cells.
J Invest Dermatol 1993 Mar
PMID:Expression of functional alpha 4 beta 1 integrin by human dermal fibroblasts. 844 Sep 15

Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are autoimmune diseases in which there is loss of cohesion between keratinocytes (acantholysis) and blistering within the epidermis. PV is characterized by acantholysis predominantly between the epidermal basal cells and suprabasal layers, whereas in PF intraepidermal cleavage is higher in the epidermis. Adhesion between keratinocytes is dependent on the function of transmembrane glycoproteins of the cadherin family present in specialized adhesion junctions, the desmosomes. The pathogenesis of acantholysis in pemphigus is uncertain, but the pemphigus autoantibodies bind to epithelial cadherins. We have used monoclonal antibodies to desmosomal components to investigate their distribution in different forms of pemphigus. Our results show that the localization of desmosomal components is abnormal in intact perilesional epidermis, intact epidermis above the blisters in PV and intact epidermis below the blisters in PF. We suggest that autoantibody binding may have a direct effect on the function of specific epithelial cadherins, but will only cause cell separation where the antigen is the principal adhesion molecule.
Br J Dermatol 1993 Apr
PMID:An immunohistological study of desmosomal components in pemphigus. 849 48

Interactions of cells with their extracellular matrix (ECM) are central to tissue-specific migration, localization, and function of migratory cells. Since mast cells circulate as immature precursor cells and home to tissues in a characteristic distribution, with increases in various disease states, we used the immature human mast cell line HMC-1 as a model to investigate the poorly understood mast cell-ECM interactions in humans. Functional adhesion studies showed that HMC-1 cells spontaneously adhere to fibronectin and laminin (80% at 6 and 12 microgram/ml, respectively) and to collagen type I and III (50% at 20 microgram/ml), whereas binding to vitronectin and collagen type IV required cell activation by phorbol myristate acetate. HMC-1 cells did not adhere to hyaluronic acid. Moreover, both fibronectin and laminin supported pronounced cytoplasmatic spreading with formation of isolated lamellipodia, whereas these cells exhibited a round cell shape on collagen and vitronectin, as shown by scanning electron microscopy. On flow cytometric analysis, HMC-1 cells expressed several adhesion molecules including the integrins beta 1, alpha 2 through alpha 6, alpha v, and alpha v beta 5, as well as CD44. Adhesion to fibronectin and vitronectin was found to be divalent cation- and arginine-glycine-aspartic acid-dependent, and could be blocked by antibodies to beta 1 or alpha 5, and alpha v or alpha v beta 5, respectively. In contrast, binding to laminin and collagen could not be blocked by monoclonal antibodies to any of the cell surface adhesion receptors expressed. Our results show that immature mast cells are able to modify their adhesive behavior in response to various ECM proteins and activating stimuli, and that this phenomenon is partly integrin mediated. These findings may be important for our understanding of the mechanisms leading to tissue-specific localization of mast cells.
J Invest Dermatol 1996 Mar
PMID:Interactions of immature human mast cells with extracellular matrix: expression of specific adhesion receptors and their role in cell binding to matrix proteins. 864 90

We report a patient with mycosis fungoides (MF) and transformation to anaplastic (CD30+) lymphoma, who developed an unusual manifestation in the breast. Cutaneous and extracutaneous tumour cells both showed marked intraepithelial migration, but had distinct expression patterns of epitheliotropism-associated integrins. Intraepidermal and dermal lymphoma cells in the skin expressed most of the integrins that are presumed to be involved in epitheliotropism, such as leucocyte functional antigen-1 (LFA-1), alpha 1 beta 1, alpha 3 beta 1, alpha 4 beta 1 and alpha 6 beta 1. In the breast, most of the extraepithelial tumour cells only expressed the laminin-5 ligand alpha 3 beta 1 (strong) and the collagen ligand alpha 1 beta 1 (weak). However, on the intraepithelial tumour cells in the mammary ducts and glands LFA-1, alpha 4 and alpha E could also be detected. In view of these findings we propose epitheliotropism of the MF cells in the breast to be a multistep process in which tumour cell-epithelial basement membrane (EBM) interaction, predominantly mediated by alpha 3 beta 1 and laminin-5, is the primary event. Adhesion to and subsequent infiltration of the neoplastic lymphoid cells into the EBM may, either directly or indirectly, lead to upregulation and/or activation of other integrins that amplify interaction with epithelial cells.
Br J Dermatol 1996 Jun
PMID:Mycosis fungoides with extracutaneous localization in the breast. 876 39

We have investigated the effect of the synthetic phospholipid analogue, hexadecylphosphocholine (HePC), a member of a new class of membrane-affecting antiproliferative drugs, on adhesion to extracellular matrix components, reorganization of three-dimensional collagen lattices, and proliferative activity of human keratinocyte populations in vitro. Six transformed keratinocyte lines were compared with their normal counterparts from interfollicular epidermis. Adhesion to collagen types I and IV, laminin, and fibronectin was weakest in normal keratinocytes (binding of 3-10% of the cells), followed by HaCaT and HaCaT-II/3 (25-30% binding), and the squamous carcinoma lines and SV-40 transformed keratinocytes (35-50% binding). Treatment with non-toxic doses of 10-20 mumol/l HePC led to a clear inhibition of the adhesive interactions by 50-75% in all populations. The impaired adhesion capacity was paralleled by a clear decrease of the ability of all keratinocyte populations to contract three-dimensional collagen lattices, an experimental model system for the reorganization of extracellular matrices. Histological examination revealed that these effects were due to a reduced cell number in the collagen lattices, a finding underscored by significant inhibition of proliferative activity of all keratinocyte populations by HePC. Furthermore, HePC led to marked changes of cellular morphology in the contracted gels. FACS analysis revealed that the impaired interaction with components of the extracellular matrix was not due to a specific downregulation of beta 1-integrins, the major cell-surface receptors for the respective matrix proteins. In conclusion, our results provide new insights into the potential action of HePC in a variety of skin disorders. Decreased proliferative activity and changes of cellular morphology, combined with impaired interactions with extracellular matrix proteins and a consecutive loss of matrix organization capacity, may cause suppression of different hyperproliferative skin diseases.
Br J Dermatol 1996 Nov
PMID:Cell-matrix interactions of normal and transformed human keratinocytes in vitro are modulated by the synthetic phospholipid analogue hexadecylphosphocholine. 897 67

Skin mast cells are typically located in the perivascular or perineural connective tissue. We observed that HMC-1 mast cells growing in suspension adhered efficiently to (> 90% of cells) and spread on top of fibroblast monolayers and to a lesser degree on purified extracellular matrix proteins. Since adhesive interactions determine cell migration and tissue localization we studied the mechanism. It was found that HMC-1 cells attach to collagen I and fibronectin, laminin, collagen IV and vitronectin, but not to collagens III and VI or hyaluronic acid. Adhesion to fibronectin, collagen I and laminin was completely inhibited by mAbs blocking beta 1-integrins, whereas adhesion of HMC-1 cells to vitronectin was inhibited by anti-alpha v-chain mAbs. However, attachment of HMC-1 cells to fibroblasts was not influenced by mAbs blocking beta 1- or alpha v-chain function, by RGD peptides or by mAbs interfering with other receptors, most notably c-kit. Identical results were obtained with normal mast cells isolated from human foreskin. These results indicate that human mast cells attach to fibroblasts independently of beta 1- or alpha v-integrins as well as of c-kit receptor-mediated mechanisms. The functional characteristics observed (i.e. only partial sensitivity to trypsin and EDTA, no increase in trypsin sensitivity by pretreatment with EDTA) suggest that cadherin receptors were not involved, and it is likely that the adhesion process observed involved not-yet-defined heterotypic cell-cell adhesion receptors.
Arch Dermatol Res 1997 Mar
PMID:Heterotypic cell-cell adhesion of human mast cells to fibroblasts. 914 35

Several studies have demonstrated that dendritic cells can be generated in vitro from CD34+ hematopoietic progenitor cells. In vivo, dendritic cells are found in many tissues and reside in direct proximity to extracellular matrix proteins. Because extracellular matrix proteins affect differentiation and location of cells in tissues, this study was designed to investigate potential effects of extracellular matrix proteins on differentiation of dendritic cells. Dendritic cells were generated from CD34+ human cord blood cells in the presence of granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha for 6 d and subsequently cultured for an additional 6-d period on tissue culture plates coated with various extracellular matrix proteins. Among the extracellular matrix proteins tested, exposure to fibronectin stimulated dendritic cell/Langerhans cell differentiation as indicated by the 50% increase of the number of cells expressing the Birbeck granule-associated marker Lag and displaying numerous Birbeck granules. Adhesion on fibronectin was shown to be specifically mediated by the integrin alpha5beta1. Because laminin and collagen were unable to cause similar changes in Langerhans cell development, these results suggest that fibronectin may cause changes affecting cellular differentiation of progenitors. Hematopoietic progenitors may exhibit maturational regulated differences in response to both matrix molecules and cytokines. The influence of combined signals emanating from a supportive microenvironment, specific integrins, and particular cytokines in the differentiation of Langerhans cells is discussed.
J Invest Dermatol 1997 Dec
PMID:Fibronectin upregulates in vitro generation of dendritic Langerhans cells from human cord blood CD34+ progenitors. 940 14

The dermal papilla of the mammalian hair follicle plays an important role in regulating and controlling the hair cycle. Distinct functional stages of dermal papilla cells (DPC) are involved in this process, thus suggesting that the dermal papilla is a highly specialized suborgan of the pilosebaceous unit. The aim of the present study was to investigate the functional properties of cultured DPC in various assays and to compare their functional properties with those of dermal fibroblasts (DFB). In monolayer cell cultures DPC showed an aggregative growth pattern, different to that of DFB, and lower proliferation rates, as compared to the controls. Adhesion assays performed using a 51[Cr]labeling method showed strong adhesion of both cell populations to collagen types I and IV, fibronectin and laminin, but DPC in vitro showed significantly higher adhesiveness to collagen type IV, a major component of the basement membrane of dermal papillae in vivo. The capacity of DPC to reorganize extracellular matrix components, as measured by gel contraction with three-dimensional collagen type I lattices, proved to be significantly lower than that of DFB and, moreover, DPC lysed the collagen lattices completely after 48 h in culture. The functional differences between DPC and DFB were paralleled by higher surface expression and synthesis levels of the beta 1, alpha 1, and alpha 5 chains of integrin adhesion receptors in DPC, as detected by fluorescence-activated cell-sorter analysis and radioimmunoprecipitation. These findings provide evidence that DPC are a highly specialized cell population, which clearly differs from another mesenchymal cell type, DFB. After their isolation and cultivation in vitro, DPC still preserve functional properties related to important steps of cell-matrix interaction involved in the hair cycle.
Arch Dermatol Res 1997 Nov
PMID:Cultured dermal papilla cells of the rat vibrissa follicle. Proliferative activity, adhesion properties and reorganization of the extracellular matrix in vitro. 945 91


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