Figure 1: SP16 Is an LRP1 Agonist

When serine protease inhibitors (SERPINs) bind the preoteases inactivating them, a conformational change occurs by which a short peptide containing a unique motif (5 to 11 amino acids) is exposed. SP16 contains alpha-1 antitrypsins (AATs) pentapeptide FVFLM responsible for binding to low-density lipoprotein receptor–related protein-1(LRP1). (A) Scheme modified from Joslin et al. (13) and Lillis et al. (3). (B) SP16 binds LRP1 in vitro, whereas SP34 does not. (C,D) SP16 inhibits NF-κB signaling induced by lipopolysaccharide (LPS) or Gp96 in THP1-XBlue-MD2-CD14 cells, and that treatment with LRP1 blocking antibody limits SP16-related inhibition. Ab = antibody; IgG = immunoglobulin G.