This program project represents an outgrowth of interest in trauma-related research which was fostered by the Trauma Reserch Center at Harborview Hospital and the Cell and Molecular Pathology Grant which existed for more than a decade in the Pathology Department. The approach is multidisciplinary, involving the Departments of Pathology, Biochemistry, Biological Structure, Physiology, Medicine and Surgery. The focus of this program project is small blood vessel injury and repair and their sequelae. This topic focuses a number of existing but separate areas of expertise on the problem of trauma. The overall aim is to bring modern cell biology approaches to the study of vascular injury following mechanical and thermal injury. The strengths of the program relate to the breadth of the disciplines involved and the techniques which span the in vivo to the in vitro and clinical physiology to molecular biology. One project examines the the physiologic sequelae of primary injury to either the endothelial and epithelial aspects of pulmonary alveoli or the endothelium of small blood vessels in the kidney. This study serves as the link between the more fundamental studies of the nature of the permeability components of vessels as well as mechanisms of injury and repair, and that situation found in the patient subjected to mechanical or thermal injury. The former studies include a study of vascular injury (Dr. Harlan), vascular repair (Dr. Gadjusek), and the cellular and matrix compositions of two vascular beds (lung - Dr. / sage, kidney - Dr. Striker). Correlations between physiological function, biochemical observation and morphology will be sought by the development of a morphometric model. Dr. Bolender, who leads this effort, will collaborate with all of the other projects. Other interactions between projcts which have not been enumerated involve sharing techniques at the biochemical and physiologic levels (Doctors Sage, Winn, Gadjusek, Harlan and Striker), cells to examine interactions (Doctors Sage, Gadjusek and Striker) and specimens from patients and animals (Doctors Winn, Gadjusek, Striker, Bolender and Harlan). We expect that the use of a multidisciplinary basic biologic approach coupled with the appropriate physiologic experiments and our close affiliation with the Trauma Center will provide a unique opportunity to correlate basic and clinical findings.