Rat C‐reactive protein activates the autologous complement system

Abstract

Activation of complement is a biological function of human C-reactive protein (hCRP), whereas rat CRP (rCRP) has been claimed to be unable to activate complement. As important biological functions of proteins are probably conserved among species, we re-evaluated, using various ligands, the capability of rCRP to activate complement. The activation of complement by hCRP and rCRP was investigated in solid- and fluid-phase systems. In the solid-phase system, purified CRP was fixed to enzyme-linked immunosorbent assay (ELISA) plates and incubated with human or rat recalcified plasma. Dose-dependent binding of human and rat C3 and C4 was observed to human and rat CRP, respectively. In the fluid-phase system, recalcified rat plasma, which contains about 500 mg/l of CRP, or human plasma supplemented with hCRP, were incubated with lyso-phosphatidylcholine. A dose-dependent activation of complement was observed upon incubation with this ligand, as reflected by the generation of activated C4 as well as of CRP-complement complexes. This activation was, in both cases, inhibited by preincubation of plasma with p-aminophosphorylcholine, a specific inhibitor of the interaction of CRP with its ligands, or by chelation of calcium ions. We conclude that rat CRP, similarly to human CRP, can activate autologous complement. These results support the notion that opsonization of ligands with complement is an important biological function of CRP.

Role of the Property of C-Reactive Protein to Activate the Classical Pathway of Complement in Protecting Mice from Pneumococcal Infection

“…A recent paper showed that neither human CRP nor rabbit CRP activated complement in serum from apolipoprotein E knockout mice, although in this case enzymatically modified low-density lipoprotein was used as the CRP ligand, not the PnC (30). Rat CRP does activate rat complement, but only if it is precipitated with PnC (28,31). Activation of complement by rat CRP occurs through the classical pathway because it binds to both rat and human C1q (31).…”

“…Rat CRP does activate rat complement, but only if it is precipitated with PnC (28,31). Activation of complement by rat CRP occurs through the classical pathway because it binds to both rat and human C1q (31). Both plaice and lumpsucker CRP activate human complement (24), and trout CRP has been shown to activate trout complement (32).…”

Disodium Disuccinate Astaxanthin (Cardax) Attenuates Complement Activation and Reduces Myocardial Injury following Ischemia/Reperfusion

“…The plasma concentration of CRP is increased in the presence of chronic inflammation, and there is a relationship between the circulating plasma concentration and subsequent cardiovascular events (de Beer et al, 1982;Yeh et al, 2001;Ridker et al, 2005). CRP is known to be involved in the local activation of the complement system (Volanakis, 1982;Diaz Padilla et al, 2003;Nijmeijer et al, 2003). Our previous studies showed that the crystalloid perfused isolated heart itself is capable of expressing mRNA and the rapid expression of complement proteins, as well as the membrane attack complex in response to ischemia/reperfusion injury (Yasojima et al, 1998).…”

Bee venom treatment reduced C-reactive protein and improved follicle quality in a rat model of estradiol valerate-induced polycystic ovarian syndrome

“…mice, rats, and humans) (9). CRP binds to pneumococcal C-polysaccharide (CPS) in humans; whereas in nonhumans, CRP binds to the surface of dead or dying cells (10). CRP which was first detected in 1930 by Tillet and Frances belongs to the pentraxin family of calcium-dependent ligand-binding plasma proteins, found in most vertebrates (e.g.…”