This proposal will investigate the pathobiology of alterations which occur in polymorphonuclear leukocytes (PMN's) during acute bacterial infection and other inflammatory reactions. Such cells are now characterized by the presence of "toxic" granulations, decreased motility, chemotaxis, phagocytosis, and increased oxidative metabolism. Information will be gathered by several approaches including: (1) investigation of cell surface properties by (a) measuring the attachment of gamma globulins or components of complement to the surfaces of toxic PMN's, employing radioactive and fluorescein markers; (b) determining the flux of monovalent cations (sodium and potassium) and the active uptake of diffusible aminoacids; (c) measuring pinocytosis of radioactive colloidal gold; (d) measuring adenylcyclase activity, phospholipase activity and quantitating levels of cyclic AMP. (2) Examination of factors which might regulate the increases in oxidative metabolism and nitroblue tetrazolium dye reduction of toxic PMN's. In addition to correlating changes of cell surface properties with oxidative metabolism, this will entail measuring the activities of NADH and NADPH oxidases and glutathione peroxidase. (3) Investigation of excessive release of lysosome constituents from toxic PMN's which might mediate tissue injury. (4) Examination for the elaboration of biologically active products from toxic PMN's which alter the physiologic or metabolic properties of normal PMN's. (5) Identification and characterization of defects of PMN function in patients with repeated bacterial infection.