Complement activation with pneumococcal antigens was studied both in vitro and after injection of the antigens into rats. Whole pneumococci of various serotypes activated C3-C9 in rat serum treated with ethyleneglycol-bis (β-aminoethyl ether)-
N,N
′-tetraacetic acid, although serotypes differed greatly in the extent of activation. Some purified pneumococcal capsular polysaccharides also activated C3-C9 in rat serum, but only when the antigens were present in concentrations of 500 to 1,000 μg/ml. Much of the activation with capsular polysaccharides was eliminated by the use of ethyleneglycol-bis (β-aminoethyl ether)-
N,N
′-tetraacetic acid. Activation of C3-C9 by capsular polysaccharides did not correlate with the level of reactivity observed with whole organisms of the same serotypes. After injection of 5 × 10
9
pneumococci (type 3 or type 4) intravenously into rats, there was a transient decline in serum C3-C9 activity, but there was no decline in C3-C9 levels after intravenous injection of 1,000 μg of type 3 or type 4 capsular polysaccharides. As determined by immunofluorescence, circulating capsular polysaccharide was deposited in several tissues, including the vascular endothelium and glomerular mesangium of the kidney. C3 was not detectable in these deposits, and there was no histological evidence of an inflammatory response. Capsular polysaccharides appear to be only weak activators of complement. Other pneumococcal antigens may be more important in the pathogenesis of hypocomplementemia in pneumococcal infection.
Alternative pathway activity of human serum was titrated by use of unsensitized rabbit erythrocytes (RE). Under the conditions of the assay, the von Krogh equation could be used to relate the proportion of RE lysed to the level of alternative pathway activity. The use of a 50% hemolytic endpoint provided maximum sensitivity in the assay. The 50% hemolytic endpoint could be calculated from a single measurement in the region of 20% to 80% lysis or RE. Factor B was required for lysis of RE in the test, but neither C2 nor C8 was limiting under the conditions of the assay. Alternative pathway activities of three sera with abnormal IgG levels were in the normal range, but normal serum absorbed with RE at 0 C before testing had diminished lytic activity with the test. Lysis of RE in acute-phase sera of 16 patients who had bacteremic pneumococcal pneumonia was significantly below normal (P < 0.01). Results with Re lysis in these patients correlated well with levels of Factor B that were measured immunochemically and with consumption of whole complement by zymosan.
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