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.