Activation of the Classic and Alternate Complement Pathways by Endotoxin

Abstract The ability of bacterial endotoxin (LPS) to activate the complement system was studied in guinea pig serum (GPS). In serum chelated with ethyleneglycol tetraacetic acid (EGTA) 10 mM, which permits alternate complement pathway activation but inhibits classic complement pathway activation, lysis of LPS-coated sheep erythrocytes (E-LPS) was inhibited. Furthermore, E-LPS could not decomplement GPS chelated with EGTA. GPS absorbed twice at 0°C with E-LPS retained normal levels of hemolytic complement (CH50) and reacted normally (as measured by CH50 depression) with both zymosan (which activates the alternate pathway) and LPS. The absorbed GPS did not react with E-LPS, whether measured by percentage of lysis of E-LPS or by CH50 depression after incubation with E-LPS. These results suggest that endotoxin is capable of activating both complement pathways but erythrocyte-associated endotoxin can activate only the classic patheay, requiring a serum factor absorbable by E-LPS at 0°C.