SAP And CRP Antagonize Selectins' Function In Inflammation

Serum amyloid P component (SAP) and C-reactive protein (CRP) are two classic short pentraxins secreted by hepatocytes in response to inflammatory challenges. Although widely used as a clinical indicator for inflammation, the functional role of circulating acute-phase proteins remains poorly understood in acute inflammation. The selectin (CD62) family of cell adhesion molecules mediates leukocyte trafficking and plays essential roles in leukocyte recruitment in host defense and innate immunity. However, the feedback mechanism for negative regulation of selectin-mediated leukocyte adhesion is currently not well understood.Here we report that SAP and CRP bound to P-, E- and L-selectins (CD62P, E and L), inhibiting selectin binding to human promyeloid HL-60 cells and neutralizing leukocyte rolling on activated capillary venules. Importantly, SAP and CRP potently suppressed infiltration and deposition of leukocytes, such as neutrophils and eosinophils, in several murine inflammatory models including allergic lung inflammation induced by ovalbumin (OVA) sensitization. Consistent with this result, leukocyte accumulation was significantly reduced in SAP transgenic mice, but dramatically exaggerated in SAP-deficient (SAP-/-) mice.Our findings thus demonstrate that acute-phase proteins, such as SAP and CRP, act as endogenous inhibitors of all three selectins for negative modulation of leukocyte trafficking during inflammation.