Interactions of C-Reactive Protein With the Complement System

Abstract

Protamine sulfate was found to consume large amounts of C selectively during preincubation with sera of individuals in the "acute phase". Marked depletion of C1, C4, and C2 with minimal, if any, depletion of C3-9, was observed. The consumption was time and temperature dependent, occurring most rapidly and extensively at 37°C, 0.10 M relative salt concentration and pH 7.5–8.0; it required calcium ions. It was mediated by a heat-stable nondialyzable factor which separated with C-reactive protein (CRP) during fractionation and purification, correlated with serum CRP levels, and, like other known reactivities of CRP, was inhibited by phosphoryl choline. Preparations of CRP purified either from serum or ascites resulted in consumption of large amounts of C1, C4, and C2 when preincubated with normal serum and protamine. We conclude that CRP is a potent activator of the C system at the level of C1, and that polycations such as protamine sulfate are substrates of CRP which can bring about this activation. It seems not unlikely that one role of CRP in health and disease involves its ability to interact with the C system.

Solid-phase classical complement activation by C-reactive protein (CRP) is inhibited by fluid-phase CRP–C1q interaction

“…One of the first identified properties of native CRP was its ability to activate the complement cascade by sequestration of C1q. In previous studies on CRP-complement interactions, indirect techniques, such as hemolytic activity [14,15], enzyme immunoassays [37] or immunohistochemistry [38] have been used. In the present study, we chose null ellipsometry to analyze the CRP-mediated complement deposition onto model PC-surfaces, a method that is direct, non-destructive, quantitative and allows the detection of early transient actors of the classical pathway, e.g.…”

“…Activation of the complement cascade is regarded as one of the main physiological functions of CRP, originally described by Kaplan and Volanakis who demonstrated consumption of hemolytic complement components in acute-phase sera mixed with pneumococcal Cpolysaccharide, and by Siegel et al using CRP-protamine complexes [14,15]. In the presence of calcium, each CRP subunit is able to complex with a PC-containing structure.…”

Human C-Reactive Protein Does Not Protect against Acute Lipopolysaccharide Challenge in Mice

“…The capacity of human CRP to bind to phosphocholine (11) and related residues that are widely present in bacteria and other pathogens, and then to precipitate soluble ligands, aggregate particulate ligands, and efficiently activate the classical complement pathway (12)(13)(14), all resemble closely the classical properties of Abs. Furthermore, there is direct evidence from model systems that CRP can protect against infection, specifically with strains of Streptococcus pneumoniae (15)(16)(17) and Haemophilus influenzae (18,19) that express phosphocholine appropriately.…”

Localization of C‐reactive protein in synovium of patients with rheumatoid arthritis

“…When CRP binds to an appropriate ligand in vitro, it can activate the complement system (8)(9)(10)(11)(12)(13). In the present study CRP was found bound to certain synovial nuclei in patients with rheumatoid arthritis.…”