LUNG COLLAGEN CROSSLINKING--BIOSYNTHESIS AND MATURATION

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Collagen crosslinking will be characterized in tendon, bone, skin, cartilage and lungs of rats. Using newly developed HPLC techniques for separation and quantitation of reduced and of nonreducible crosslinks, we intend to study turnover of different crosslinks in vivo. Precursor-product relationships will be defined in different tissues containing different collagen types. We will specifically test the hypothesis that certain key crosslinks are markers of the ultimate metabolic fate of collagen-degradation or deposition as fibers. Maturation of difunctional crosslinks to tri- and tetrafunctional products will be closely examined to ascertain the role of nonreducible crosslinks in the maturation process. These studies should allow us to begin to understand aspects of collagen deposition in the extracellular matrix of the lung in normal animals, and should serve as the requisite data base to allow systematic study of aberrations in these processes secondary to pathophysiology and disease.