C‐reactive protein and C1q regulate platelet adhesion and activation on adsorbed immunoglobulin G and albumin

Abstract

Blood platelets and C-reactive protein (CRP) are both used clinically as markers of ongoing inflammation, and both participate actively in inflammatory responses, although the biological effects are still incompletely understood. Rapidly adhering platelets express receptors for complement factor 1q (C1q) and the Fc part of immunoglobulin G (IgG), and CRP is known to activate/ regulate complement via C1q binding, and to ligate FccRs. In the present study, we used normal human IgG pre-adsorbed to a well-characterized methylated surface as a model solid-phase immune complex when investigating the effects of CRP and C1q on platelet adhesion and activation. Protein adsorption was characterized using ellipsometry and polyclonal antibodies, and human serum albumin (HSA) and non-coated surfaces were used as reference surfaces. Platelet adhesion to IgG and HSA was inhibited by both C1q and CRP. Furthermore, CRP (moderately) and C1q (markedly) decreased the spreading of adhering platelets. The combination of C1q and CRP was slightly more potent in reducing cell adhesion to IgG, and also impaired the adhesion to HSA and non-coated surfaces. Platelet production of thromboxane B2 (TXB 2 ) was also reduced by C1q both in the presence and absence of CRP, whereas CRP alone had no effect on TXB 2 production. We conclude that CRP and C1q regulate the behaviour of platelets, and that this may be an important immunoregulatory mechanism during inflammatory conditions.

Mutations of C-Reactive Protein (CRP) -286 SNP, APC and p53 in Colorectal Cancer: Implication for a CRP-Wnt Crosstalk

“…Besides hepatocytes, extrahepatic cells are also able to secrete CRP locally in response to inflammatory stimuli. Moreover, triggers enriched in inflammatory loci will induce prompt conformation changes in the pentameric CRP post its in situ production [44]–[49], to release the full potential in ligand binding [47], [48], [50], complement regulation [46], [48], [51]–[54] and stimulation of proinflammatory and angiogenic cell responses [48], [49], [55]–[61]. As such, the local abundance of CRP and its interactions with the stressful microenvironment should be more relevant to disease progression; while circulating CRP levels mainly mirror the underlying inflammatory status.…”

The non-classical functions of the classical complement pathway recognition subcomponent C1q

“…C1q can inhibit platelet adhesion to adsorbed IgG to a considerable extent and also decrease the spreading of the adhered platelets, which consequently would prevent atherosclerosis [76]. C1q and C-reactive protein (CRP) when added together show increased reduction in platelet adhesion to IgG than C1q alone.…”

Altered glycosylation of complexed native IgG molecules is associated with disease activity of systemic lupus erythematosus

“…28 Thus, we used ellipsometry to confirm the adsorption of F(ab') 2 -fragments and serum IgG onto surfaces of methylated (hydrophobic) silicon as previously described. 29,30 Measurements were performed on: (1) bare methylated surface; (2) with F(ab') 2 -fragments adsorbed; (3) with sera adsorbed to F(ab') 2 -fragments.…”