OVERALL GOALS: Our long term objective remains to define the biological role of C-reactive protein (CRP) in reactions of inflammation, repair, tissue destruction and resistance, with emphasis on its interrelationships with host defense mechanisms and its role in the acute phase response. As the major current thrust in this direction, we have proposed in this grant to evolve methods for large-scale purification and characterization of chemically pure biologically active material; to define aspects of the structure of CRP which relate to its function; and to define and delineate the interrelationships of CRP with its binding specificities and with the complement system. As outgrowths of these investigations we have proposed to study the interactions of CRP with lymphocytes and phagocytic cells; its interactions with normal and modified membranes; and certain of its interrelationships with other acute phase reactants in host defense and inflammation, with initial emphasis upon the amyloid P component (which we have found to show marked homology to CRP) and the alpha-1-acid glycoprotein. We hope in these ways to contribute to an understanding of the functions and role of CRP and the acute phase response in reactions of host defense, inflammation and disease.