Scavenger endothelial cells

The main function of the scavenger endothelial cells (SEC) is to remove soluble waste macromolecules from the circulation by receptor-mediated endocytosis. Potentially harmful soluble waste macromolecules are constitutively released to the body fluids dur ing normal growth and turnover of tissues and cells, as well as in inflammatory processes and tumor growth. Many of these molecules are too large to be excreted by the kidney, and are eliminated by cellular uptake and lysosomal processing. In mammals, the burden of elimination of waste macromolecules that are released from the tissues is probably shared between cells of the lymph nodes and SEC. Based on results from earlier publications, along with findings published by others, we propose t he general pri nciple that vertebrate SEC carry out receptor-mediated endocytosis at very high capacity, and degrade endocytosed macromolecules anaerobically to lactate and acetate, that are used as mitochondrial fuel in neighboring high energy consuming p arenchymal ce lls. According to this hypothesis SEC in cod supply cardiomyocytes with energy metabolites to produce ATP for contraction and associated metabolic events, whereas SEC in terrestrial vertebrates deliver high energy metabolites to liver parench ymal cells f or their production of ATP needed for biosynthesis and other high energy consuming biochemical processes. The major aim of the present project proposal is to establish the role of scavenger endothelial cells (SEC) in the local supply of energy metabolites for ATP production in neighboring high energy consuming parenchyme. To this end studies will be carried o ut to investigate 1) the catabolic fate of endocytosed hyaluronan, ndogen and collagen alpha chains in SEC in vitro, 2) the role of SEC in co d heart energy metabolism, and 3) the catabolic fate of radiolabeled hyaluronan and nidogen in mammalian ly mph nodes. idogen in mammalian ly