This Program Project has the overall objective of defining for the lung the chemical, cellular and physiological characteristics of tissue structure which predispose the lung to injury in vivo. A major portion of the investigation concerns the definition of the content, composition and in vivo functions of the connective tissue components, elastin, collagen, glycosaminoglycans and fibronectin. Studies of the mechanisms of tissue injury to the lung are focused on proteolysis, the inhibition of proteolysis, the relationship between connective tissue degradation and resynthesis. An extension of this objective is to define the spatial interrelationships ultrastructurally in situ of connective tissue components in normal lung structure and after proteolytic injury and repair. A related aspect of the overall investigation involves the identification of the specific cells and of their biochemical functions through cell culture techniques, to determine the cellular processes which contribute to connective tissue repair and the pathogenic mechanisms which lead to irreversible structural alterations in lung architecture. The relationship is also being defined between mechanical stress strain and pressure volume characteristics of the microarchitecture of alveolar wall and the connective tissue composition and structure. A part of this study concerns the role of specific cells in the mechanical, metabolic and physiological function of the lung in the process of lung cell contractility with particular reference to lung endothelium. The function of lung endothelium is also being investigated with respect to the role of lung parenchyma in the metabolic state of vasoactive substances including inins which are transported through the mixed venous circulation to the lung or elaborated in lung tissue. This aspect of the study forms an important link between the cellular functions of lung parenchyma in the role of the lung in the homeostatic and pathogenic mechanisms involving the lung in relation to vasomotor control in the whole organism.
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