The adhesion mediated by the P-selectin P-selectin glycoprotein ligand-1 (PSGL-1) couple is stronger for shorter PSGL-1 variants

Interactions between P-sel and the PSGL-1 mediate the earliest adhesive events during an inflammatory response. Human PSGL-1 displays a high degree of genetic polymorphism that has been diversely associated with susceptibility to human diseases. In the central part of PSGL-1, a 10-aa motif is repeated 14, 15, or 16 times. Moreover, two mutations, M62I and M274V, are often found giving the most common variant M62-M274 with 16 motifs (M16M) and its variants I62-M274 (I16M). Two other variants exist with 15 repeated motifs (M62M274; M15M) and with 14 motifs (M62-V274; M14V). We investigated the potential difference in the adhesive properties between these natural variants stably expressed in the HEK cell line by using the BFP technique. Their interactions with P-sel were found to be of catch bond-type, and the dissociation force was primarily dependent on the number of decameric motifs: the shorter the PSGL-1, the larger the bond strength. Finally, we found that the M62I mutation, which is close to the binding site to P-sel, reduced the adhesiveness to P-sel effectively. Collectively, these data shed new light on the polymorphism of PSGL-1 and could help the research on its associations to human pathologies. J. Leukoc. Biol. 87: 727-734; 2010.