Rat C-reactive protein activates the autologous complement system.
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.
Diaz Padilla
Niubel
N
Department of Immunopathology, Sanquin Research, and Laboratory for Experimental and Clinical Immunology, Academical Medical Center, University of Amsterdam, Amsterdam, The Netherlands. N.diaz@sanquin.nl
Bleeker
Wim K
WK
Lubbers
Yvonne
Y
Rigter
Gemma M M
GM
Van Mierlo
Gerard J
GJ
Daha
Mohamed R
MR
Hack
C Erik
CE
D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D002097:C-Reactive Protein / Q000276:immunology*; D003167:Complement Activation / Q000276:immunology*; D003176:Complement C3 / Q000276:immunology; D003181:Complement C4 / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D008024:Ligands; D008244:Lysophosphatidylcholines / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000276:immunology; D051381:Rats
D003176:Complement C3; D003181:Complement C4; D008024:Ligands; D008244:Lysophosphatidylcholines; D011135:Polysaccharides, Bacterial; C027158:polysaccharide C-substance (Streptococcus); D002097:C-Reactive Protein