Abstract
Pneumococci activate the alternative complement (C) pathway in the absence of demonstrable antibody in normal guinea pig serum. They also activate the classical C pathway in the presence of type-specific antibody and perhaps through other mechanisms as well. A quantitative examination was undertaken of the roles of these 2 pathways of C activation in the splanchnic sequestration of 125I-labeled pneumococci, using a-guinea pig model of pneumococcal bacteremia. Normal unimmunized guinea pigs (NIH-GP) localized more than 3 times as many pneumococci to the liver as the spleen during a period when exponential bloodstream clearance was occurring. C4-deficient guinea pigs (C4D-GP) and cobra venom factor-treated guinea pigs (CVF-GP) showed progressively fewer pneumococci cleared by the liver with concomitant increases in the extent of splenic uptake, demonstrating the important role of C in the clearance of bacteria in the unimmunized animal. Immunization of guinea pigs brought about an increase in pneumococcal sequestration by the liver in NIH and C4D-GP but did not affect the localization pattern of CVF-GP. A comparison of reticuloendothelial system (RES) localization patterns with the rate of removal of bacteria from the bloodstream showed a highly significant correlation between increases in splenic sequestration and persistence of bacteremia. Thus, opsonization by C is an important determinant of the RES clearance of pneumococci. Unlike RBC clearance, where C plus IgM leads to hepatic localization, and C plus IgG tends to produce splenic localization, C in the presence or absence of type-specific antibody tends to cause hepatic localization of pneumococci. When C-mediated opsonic activity is less than optimal, the slower clearance of bacteremia that results is accompanied by an increased dependence on splenic sequestration of pneumococci.
