Activation of leukocyte function-associated antigen-1 on adult T-cell leukemia cells. 1999

Y Tanaka
The First Department of Internal Medicine, University of Occupational and Environmental Health, Japan, School of Medicine, Kitakyushu. tanaka@med.uoeh-u.ac.jp

Adult T cell leukemia (ATL) is characterized by massive infiltration of circulating ATL cells into a variety of tissues, a finding often associated with poor prognosis. Leukocyte migration from circulation into tissue depends on integrin-mediated adhesion to endothelium and integrins are tightly regulated by several stimuli such as inflammatory chemokines. We have investigated the mechanisms of extravasation of ATL cells and reported the novel features of endogenous chemokine-induced adhesion of ATL cells to the endothelium. We propose that ATL cells adhere to endothelial cells through an adhesion cascade similar to normal leukocytes, and that the chemokines produced by ATL cells are involved in triggering integrin LFA-1 through cytoskeletal rearrangement induced by G-protein-dependent activation of PI 3-kinases in an autocrine manner. Furthermore, the cell surface heparan sulfate proteoglycan particularly on ATL cells is involved in chemokine-dependent autocrine stimulation of integrin-triggering by immobilizing the chemokine on them. These events result in a strong adhesion of ATL cells to the endothelium and spontaneous transendothelial migration.

UI MeSH Term Description Entries
D002448 Cell Adhesion Adherence of cells to surfaces or to other cells. Adhesion, Cell,Adhesions, Cell,Cell Adhesions
D003599 Cytoskeleton The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. Cytoplasmic Filaments,Cytoskeletal Filaments,Microtrabecular Lattice,Cytoplasmic Filament,Cytoskeletal Filament,Cytoskeletons,Filament, Cytoplasmic,Filament, Cytoskeletal,Filaments, Cytoplasmic,Filaments, Cytoskeletal,Lattice, Microtrabecular,Lattices, Microtrabecular,Microtrabecular Lattices
D004730 Endothelium, Vascular Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components. Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013601 T-Lymphocytes Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T Cell,T Lymphocyte,T-Cells,Thymus-Dependent Lymphocytes,Cell, T,Cells, T,Lymphocyte, T,Lymphocyte, Thymus-Dependent,Lymphocytes, T,Lymphocytes, Thymus-Dependent,T Cells,T Lymphocytes,T-Cell,T-Lymphocyte,Thymus Dependent Lymphocytes,Thymus-Dependent Lymphocyte
D015459 Leukemia-Lymphoma, Adult T-Cell Aggressive T-Cell malignancy with adult onset, caused by HUMAN T-LYMPHOTROPIC VIRUS 1. It is endemic in Japan, the Caribbean basin, Southeastern United States, Hawaii, and parts of Central and South America and sub-Saharan Africa. ATLL,HTLV I Associated T Cell Leukemia Lymphoma,HTLV-Associated Leukemia-Lymphoma,HTLV-I-Associated T-Cell Leukemia-Lymphoma,Human T Lymphotropic Virus Associated Leukemia Lymphoma,Human T Lymphotropic Virus-Associated Leukemia-Lymphoma,Human T-Cell Leukemia-Lymphoma,Leukemia Lymphoma, Adult T Cell,Leukemia Lymphoma, T Cell, Acute, HTLV I Associated,Leukemia, Adult T-Cell,Leukemia-Lymphoma, T-Cell, Acute, HTLV-I-Associated,T Cell Leukemia Lymphoma, HTLV I Associated,T Cell Leukemia, Adult,T-Cell Leukemia, Adult,T-Cell Leukemia-Lymphoma, Adult,T-Cell Leukemia-Lymphoma, HTLV-I-Associated,Adult T-Cell Leukemia,Adult T-Cell Leukemia-Lymphoma,Adult T-Cell Leukemia-Lymphomas,Adult T-Cell Leukemias,HTLV Associated Leukemia Lymphoma,HTLV-Associated Leukemia-Lymphomas,HTLV-I-Associated T-Cell Leukemia-Lymphomas,Human T Cell Leukemia Lymphoma,Human T-Cell Leukemia-Lymphomas,Leukemia, Adult T Cell,Leukemia-Lymphoma, HTLV-Associated,Leukemia-Lymphoma, HTLV-I-Associated T-Cell,Leukemia-Lymphoma, Human T-Cell,Leukemia-Lymphomas, Adult T-Cell,Leukemia-Lymphomas, HTLV-Associated,Leukemia-Lymphomas, HTLV-I-Associated T-Cell,Leukemia-Lymphomas, Human T-Cell,Leukemias, Adult T-Cell,T Cell Leukemia Lymphoma, Adult,T-Cell Leukemia-Lymphoma, Human,T-Cell Leukemia-Lymphomas, Adult,T-Cell Leukemia-Lymphomas, HTLV-I-Associated,T-Cell Leukemia-Lymphomas, Human,T-Cell Leukemias, Adult
D016023 Integrins A family of transmembrane glycoproteins (MEMBRANE GLYCOPROTEINS) consisting of noncovalent heterodimers. They interact with a wide variety of ligands including EXTRACELLULAR MATRIX PROTEINS; COMPLEMENT, and other cells, while their intracellular domains interact with the CYTOSKELETON. The integrins consist of at least three identified families: the cytoadhesin receptors (RECEPTORS, CYTOADHESIN), the leukocyte adhesion receptors (RECEPTORS, LEUKOCYTE ADHESION), and the VERY LATE ANTIGEN RECEPTORS. Each family contains a common beta-subunit (INTEGRIN BETA CHAINS) combined with one or more distinct alpha-subunits (INTEGRIN ALPHA CHAINS). These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development; HEMOSTASIS; THROMBOSIS; WOUND HEALING; immune and nonimmune defense mechanisms; and oncogenic transformation. Integrin
D016169 Lymphocyte Function-Associated Antigen-1 An integrin heterodimer widely expressed on cells of hematopoietic origin. CD11A ANTIGEN comprises the alpha chain and the CD18 antigen (CD18 ANTIGENS) the beta chain. Lymphocyte function-associated antigen-1 is a major receptor of T-CELLS; B-CELLS; and GRANULOCYTES. It mediates the leukocyte adhesion reactions underlying cytolytic conjugate formation, helper T-cell interactions, and antibody-dependent killing by NATURAL KILLER CELLS and granulocytes. Intracellular adhesion molecule-1 has been defined as a ligand for lymphocyte function-associated antigen-1. LFA-1,Leukocyte Function Associated Antigen-1,Integrin alphaLbeta2,Antigen-1, Lymphocyte Function-Associated,Lymphocyte Function Associated Antigen 1,alphaLbeta2, Integrin
D018925 Chemokines Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C; (CHEMOKINES, C); CC; (CHEMOKINES, CC); and CXC; (CHEMOKINES, CXC); according to variations in a shared cysteine motif. Chemokine,Chemotactic Cytokine,Chemotactic Cytokines,Cytokines, Chemotactic,Intercrine,Intercrines,Cytokine, Chemotactic
D019812 Heparan Sulfate Proteoglycans Ubiquitous macromolecules associated with the cell surface and extracellular matrix of a wide range of cells of vertebrate and invertebrate tissues. They are essential cofactors in cell-matrix adhesion processes, in cell-cell recognition systems, and in receptor-growth factor interactions. (From Cancer Metastasis Rev 1996; 15(2): 177-86; Hepatology 1996; 24(3): 524-32) HSPG,Heparan Sulfate Proteoglycan,Proteoheparan Sulfate,Proteoglycan, Heparan Sulfate,Proteoglycans, Heparan Sulfate,Sulfate Proteoglycans, Heparan

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