Comparison of mouse and human leukocyte ligands for endothelial selectins
| . | Mouse . | Human . | ||
|---|---|---|---|---|
| Function . | Evidence . | Function . | Evidence . | |
| PSGL-1 (PMN and T cells) | Tethering to and rolling on P- and E- selectin | Antibody blocking, and knockout mice, flow chamber and IVM | Tethering to and rolling on P-selectin | Antibody blocking, flow chamber |
| Signaling, β2 integrin activation for slow rolling on P- and E-selectin | Flow chamber and IVM | Signaling, integrin activation for slow rolling on E-selectin | Antibody blocking, flow chamber | |
| CD44 (PMN and T cells) | Cooperates with PSGL-1 for rolling on E-selectin | IVM, flow chamber | Contributes to binding to fluid-phase E-selectin | Flow cytometry |
| Signaling for β2 integrin activation and slow rolling on E-selectin | Knockout mice, flow chamber, IVM | |||
| Signaling for receptor clustering on E-selectin | Knockout mice, IVM | |||
| Cooperates with PSGL-1 for leukocyte migration during inflammation | Inflammatory models in knockout mice | |||
| ESL-1 (PMN) | Present on the surface of neutrophils and Th1 lymphocytes | Surface biotinylation and Western blotting | Not detected on the surface of human leukocytes | Surface biotinylation and Western blotting |
| Binds to E-selectin | E-selectin affinity columns | Unknown contribution to E-selectin binding | ||
| Antibody blocking on myeloid cell line | ||||
| Cooperates with PSGL-1 for tethering to E-selectin Cooperates with CD44 for slow rolling on E-selectin Allows steady rolling on E-selectin Signaling for β2 integrin activation | shRNA silencing and IVM | |||
| CD43 (T cells) | Cooperates with PSGL-1 for binding to E-selectin | Flow cytometry and static adhesion in knockout mice | Supports binding and rolling of E-selectin-expressing cells | In vitro binding and blot-rolling assays |
| Cooperates with PSGL-1 for Th1 cell migration during inflammation | Skin inflammation model in knockout mice | |||
| L-selectin (PMN) | Does not bind to P- or E-selectin | E-selectin affinity columns and antibody blocking | Binding to E-selectin | E-selectin affinity columns |
| Binding to PSGL-1 mediates secondary tethers | Flow chamber and IVM in knockout mice | Mediates rolling on E-selectin | Flow chamber and antibody blocking | |
| Glycolipids (PMN) | Unknown contribution to selectin binding | Ligands for P- and E-selectin are protease-sensitive | Mediate rolling of E-selectin expressing cells | Flow chamber and use of inhibitors of glycosphingolipid biosynthesis |
| Other differences (PMN and T cells) | Ligands for P- and E-selectin are protease sensitive | Ligands for E-selectin are protease insensitive | ||
| Antibodies to sLex and Lex do not bind murine neutrophils | Antibodies to sLex and Lex strongly bind to human neutrophils | |||
| PSGL-1, CD43, CD44 and ESL-1 cooperate for tethering, rolling and migration to inflamed sites | Knockout and shRNA silencing using IVM, and inflammation models | Unknown repertoire of E-selectin ligands; in vitro evidence exists for PSGL-1, CD44, L-selectin, and glycolipids on neutrophils; evidence for PSGL-1 and CD43 on T cells | ||
| . | Mouse . | Human . | ||
|---|---|---|---|---|
| Function . | Evidence . | Function . | Evidence . | |
| PSGL-1 (PMN and T cells) | Tethering to and rolling on P- and E- selectin | Antibody blocking, and knockout mice, flow chamber and IVM | Tethering to and rolling on P-selectin | Antibody blocking, flow chamber |
| Signaling, β2 integrin activation for slow rolling on P- and E-selectin | Flow chamber and IVM | Signaling, integrin activation for slow rolling on E-selectin | Antibody blocking, flow chamber | |
| CD44 (PMN and T cells) | Cooperates with PSGL-1 for rolling on E-selectin | IVM, flow chamber | Contributes to binding to fluid-phase E-selectin | Flow cytometry |
| Signaling for β2 integrin activation and slow rolling on E-selectin | Knockout mice, flow chamber, IVM | |||
| Signaling for receptor clustering on E-selectin | Knockout mice, IVM | |||
| Cooperates with PSGL-1 for leukocyte migration during inflammation | Inflammatory models in knockout mice | |||
| ESL-1 (PMN) | Present on the surface of neutrophils and Th1 lymphocytes | Surface biotinylation and Western blotting | Not detected on the surface of human leukocytes | Surface biotinylation and Western blotting |
| Binds to E-selectin | E-selectin affinity columns | Unknown contribution to E-selectin binding | ||
| Antibody blocking on myeloid cell line | ||||
| Cooperates with PSGL-1 for tethering to E-selectin Cooperates with CD44 for slow rolling on E-selectin Allows steady rolling on E-selectin Signaling for β2 integrin activation | shRNA silencing and IVM | |||
| CD43 (T cells) | Cooperates with PSGL-1 for binding to E-selectin | Flow cytometry and static adhesion in knockout mice | Supports binding and rolling of E-selectin-expressing cells | In vitro binding and blot-rolling assays |
| Cooperates with PSGL-1 for Th1 cell migration during inflammation | Skin inflammation model in knockout mice | |||
| L-selectin (PMN) | Does not bind to P- or E-selectin | E-selectin affinity columns and antibody blocking | Binding to E-selectin | E-selectin affinity columns |
| Binding to PSGL-1 mediates secondary tethers | Flow chamber and IVM in knockout mice | Mediates rolling on E-selectin | Flow chamber and antibody blocking | |
| Glycolipids (PMN) | Unknown contribution to selectin binding | Ligands for P- and E-selectin are protease-sensitive | Mediate rolling of E-selectin expressing cells | Flow chamber and use of inhibitors of glycosphingolipid biosynthesis |
| Other differences (PMN and T cells) | Ligands for P- and E-selectin are protease sensitive | Ligands for E-selectin are protease insensitive | ||
| Antibodies to sLex and Lex do not bind murine neutrophils | Antibodies to sLex and Lex strongly bind to human neutrophils | |||
| PSGL-1, CD43, CD44 and ESL-1 cooperate for tethering, rolling and migration to inflamed sites | Knockout and shRNA silencing using IVM, and inflammation models | Unknown repertoire of E-selectin ligands; in vitro evidence exists for PSGL-1, CD44, L-selectin, and glycolipids on neutrophils; evidence for PSGL-1 and CD43 on T cells | ||
Listed are glycoconjugates with strong evidence as P- or E-selectin ligands in at least some assays. The leukocyte subset (neutrophils, PMN; or T lymphocytes) for which the function of each putative ligand has been best studied is indicated in parentheses.
IVM indicates intravital microscopy; sLex, sialyl Lewis x structure; and Lex, Lewis x structure.