Splenectomy predisposes individuals to overwhelming infections, particularly with encapsulated organisms of which the pneumococcus is the most common. Pneumococcal sepsis usually occurs after invasion from the respiratory tract. Successful eradication of bacteria inoculated into the alveoli depends upon phagocyte function, and alveolar macrophages and granulocytes play different roles depending on bacteria virulence and size of the inoculum. This proposal is designed to elucidate the role of the spleen in modifying pulmonary bacterial clearance in the early period after bacterial challenge. Clearance of pneumococci and other bacteria will be examined systematically using radiolabelled bacteria by enumerating the number of viable bacteria remaining in the lungs of splenectomized and sham operated mice at various times following pulmonary inoculation as well as determining the amount of radioactive material remaining in the lungs at various times. Cells will be harvested from the lungs and the pool size of alveolar macrophages and granulocytes will be enumerated over time to determine if splenectomy impairs this response. In addition, the numbers of macrophones and granulocytes associated with bacteria will be enumerated to give a further assessment of in vivo phagocytic function and the relative contribution of macrophages and granulocytes. in vitro phagocytic and bactericidal function of pulmonary macrophages from unexposed mice will be examined both following splenectomy and sham operation. Manipulations which may improve survival following bacterial challenge after splenectomy, such as autotransplantation of splenic tissue, immunization with pneumococcal polysaccharide vaccines, and the use of immunomodulators will be examined alone and in various combinations for effects on pulmonary bacteria clearance and phagocytic cellular response in function as well as survival. Observations made from these investigations will help direct further investigations into the pathogenesis of overwhelming infections after splenectomy, and may provide some direction toward the development of new therapies with clinical usefulness.
