The C‐terminal hexapeptide in C‐reactive protein inhibits neutrophil adhesion to endothelial cells through CD32

Abstract

The role of C-reactive protein (CRP) as a regulator of inflammation is incompletely understood. Structural rearrangement in CRP results in expression of potent pro-inflammatory actions and renders the molecule susceptible to proteolysis, yielding the C-terminal peptide Lys-Pro-Gln-Leu-Trp-Pro (CRP peptide 201–206). We investigated the impact of this peptide on neutrophil interactions with endothelial cells. CRP peptide 201–206 induced L-selectin shedding from human neutrophils and inhibited L-selectin-mediated neutrophil adhesion to TNF-á-activated human coronary artery endothelial cells. CRP peptide 201–206 did not activate endothelial cells. Antibodies against CD32 but CD16 or CD64 prevented the actions of CRP peptide 201–206. Substitution of Lys-201, Gln-203 or Trp-205 with Ala resulted in loss of the biological activities, whereas mutation of Pro-202, Leu-204 or Pro-206 did not affect biological activities. Our results identify amino acid residues involved in CRP peptide 201–206 signaling through CD32, which limits neutrophil adhesion to endothelial cells, and open up new perspectives for limiting inflammation. (Grant support: CIHR MOP-94851).