Interactions of C reactive protein with the complement system. II. C reactive protein mediated consumption of complement by poly L lysine polymers and other polycations

Abstract

Cationic homopolymers of poly L lysine were found to activate complement (C) via C reactive protein (CRP) and deplete C3 and C5 as well as early acting C components. Maximum C consumption was obtained with polymers of 2,000-8,000 daltons; polymers of 1,700, 11,000, and 23,000 daltons were intermediate in reactivity, while L lysine, lysyl L lysine, tetra L lysine, and polymers of 70,000-400,000 daltons lacked significant C consuming activity. Naturally occurring polycations which consumed C in the presence of CRP included myelin basic proteins, cationic proteins of rabbit leukocytes, and both lysine and arginine rich histones; poly L arginine polymers of 17,000 but not 65,000 daltons also were C consuming. Polycations without such reactivity included poly L ornithine (5,000 and 165,000 daltons), egg white and human lysozymes, and Polybrene. The polycations which failed to induce C consumption via CRP, inhibited its consumption by both active polycations and by C polysaccharide (CPS). The relative inhibitory capacity of phosphorylcholine and polycations in CPS and polycations CRP systems was consistent with the concept that phosphate esters and polycations react at the same or an overlapping combining site. The ability of certain polycations to activate C via CRP increases the potential for initiation of host reactions via C. The capacity of other polycations to inhibit C activation via CRP introduces a potential for physiologic or pharmacologic manipulation. These considerations would seem to expand the potential role of CRP in the initiation and modulation of the inflammatory response.