IDENTIFICATION AND CHARACTERIZATION OF THE FUNCTIONAL MOLECULE MEMBRANE CD 38 IN LIVER CELLS STAR -Author:
MARCH RIERA SANDRA.
Year:
2005.
University:
BARCELONA [
www.ub.es].
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.
Summary: The star-liver cells (CHE) represent between 5-8% of all liver cells. They are located in the space of Diese (virtual space between endothelial cells and parequima). In the normal liver, have a phenotype quiescent, morphologically characterized by the presence of vacuolas intracitiplasmaticas containing vitamin A. In the normal liver are functionally involved in: A-Regulation of parts of the extracellular matrix. B-secretion of a variety of cytokines and growth factors. C-Control diameter of the sinusoids. D-Storage vitamin In situations of tissue injury CHE suffer the activation process and acquiring a transformed phenotype type miofibroblasto with characteristics of this lineage: a high proliferative capacity, synthetic and contractile. In this state of activation CHE are involved in the processes of fibrogenesis, to be the main producers of extracellular matrix in inflammatory processes, due to their ability to secrete soluble mediators in the middle of inflammation (eg Quimioquinas, hematopoietic growth factors, etc.). processes and contraction, CHE are able to concentrate or relax in response to various vasoactive substances. Our goal was to identify new molecules expressed on the surface CHE and then study their possible role in functional processes fisopatológicos as inflammation, fibrogenesis and contraction. To achieve this objective we will continue the strategy was the production of monoclonal antibodies that recognize proteins on the membrane expressed mainly in Che. The results were as follows: 1-It has identified the molecule CD38 in the cell membrane star-liver. 1.1, - CD38 is expressed on a baseline liver cells and its star-term increases after activating both "in vivo" and "in vitro". 1.2, - CD38 present in the cell membrane liver star - has an approximate weight of 50KD and a tenth is in the form of dímero. 2, - CD38 is involved in the activation of liver cells star-affecting different functions. 2.1 - The intersecting of CD38 induces the mobilization of intracellular calcium in the star-liver cells. 2.2, - CD38 induces secretion of IL-6 regardless of the state of activation of the star-liver cells. 2.3-CD38 induces the expression of adhesion molecules I-CAM, V-CAM and N-CAM in liver cells activated for star-not in quiescent (dependent activation state). 2.4-CD38 in vitro induced concentration of star-liver cells in culture, the phosphorylation of myosin light chain and cytoskeletal reorganization and in vivo induces an increase of portal pressure in rats. 2.5-CD38 inhibie the synthesis of collagen I and II metalloproteinase (MMP-2) the effects are different depending on the state of activation of the cell. These results indicate that CD38 is involved in inflammation processes, and contraction mediated fibrogenesis star-liver cells.