C-reactive protein-derived peptide 201-206 inhibits neutrophil adhesion to endothelial cells and platelets through CD32

The role of CRP as a regulator of inflammation is not fully understood. Structural rearrangement in CRP results in expression of potent proinflammatory actions. Proteolysis of CRP yields the C-terminal peptide Lys ²⁰¹-Pro-Gln-Leu-Trp-Pro ²⁰⁶. Here, we investigated the impact of this peptide on neutrophil interactions with endothelial cells and platelets, critical inflammatory events triggering acute coronary artery disease. CRP peptide 201-206 induced L-selectin shedding from human neutrophils and inhibited L-selectin-mediated neutrophil adhesion to TNF-α-activated HCAECs under nonstatic conditions. CRP peptide 201-206 also attenuated shear-induced up-regulation of platelet P-selectin expression, platelet capture of neutrophils, and subsequent homotypic neutrophil adhesion in human whole blood. Anti-CD32 but not anti-CD16 or anti-CD64 mAb effectively prevented the inhibitory actions of CRP peptide 201-206. Substitution of Lys ²⁰¹, Gln ²⁰³, or Trp ²⁰⁵ with Ala in CRP peptide 201-206 resulted in loss of the biological activities, whereas peptides in which Pro ²⁰², Leu ²⁰⁴, or Pro ²⁰⁶ was substituted with Ala retained biological activity. We identified amino acid residues involved in CRP peptide 201-206-FcγRII (CD32) interactions, which mediate potent antineutrophil and antiplatelet adhesion actions, and these findings open up new perspectives for limiting inflammation and thrombosis underlying coronary artery disease.