Interaction of C-Reactive Protein Complexes with the Complement System

Abstract

Abstract The reaction of C-reactive protein (CRP)-positive sera and crystalline CRP with pneumococcal C-polysaccharide at equivalence induced consumption of human complement and C3 conversion in the absence of detectable antibody. Sera with negative or trace reaction for CRP most often gave no or minimal consumption of complement on addition of C-polysaccharide. Analysis of complement components consumed in the reaction of CRP-positive sera with C-polysaccharide, in the absence of detectable antibody, demonstrated consumption of 80% or more of total hemolytic complement, C1, C4, and C2, and 42 to 66% consumption of C3-9. Quantitative estimates of the minimal amount of CRP in acute phase sera which permitted fixation of complement closely approximated the minimal value obtained with crystalline CRP. All normal human sera tested permitted consumption of complement by CRP complexes, including sera from infants 5 to 7 months of age with physiologic hypogammaglobulinemia and sera previously absorbed with pneumococcal cell walls to remove any presumptive trace of antibody to C-polysaccharide. Both the CRP-C-polysaccharide precipitation and complement consumption reactions were 100% inhibited by phosphoryl choline but were not at all inhibited by N-acetyl galactosamine, the major determinant of antibody specificity. CRP reacted with phosphoryl choline of the choline phosphatides, lecithin and sphingomyelin, by complement fixation and by flocculation. Immunodiffusion analysis of the washed complexes obtained by reaction of CRP-positive sera with C-polysaccharide and with lecithin demonstrated strong lines of precipitation for CRP, C1q, and C3, whereas immunoglobulins were absent or detectable only in faint traces. These combined data have permitted the conclusion that complement consumption was attributable to CRP complexes and that it proceeded via the classical pathway independent of the presence of specific antibody or immunoglobulin. The specificity of CRP for choline phosphatides and its capacity to activate the complement system are considered in relation to the possible functions of CRP in the inflammatory process.