Selectin-carbohydrate interactions during inflammation and metastasis

L-, E-, and P-selectin are membrane-anchored, C-type lectins that initiate tethering and rolling of flowing leukocytes on endothelial cells, platelets, or other leukocytes during inflammation. The selectins bind to sialylated, fucosylated, or, in some cases, sulfated glycans on glycoproteins, glycolipids, or proteoglycans. However, they bind with relatively high affinity or avidity to only a few, appropriately modified glycoproteins on leukocytes or endothelial cells. One leukocyte mucin, PSGL-1, tethers flowing leukocytes to P-selectin on activated platelets or endothelial cells, and also helps tether leukocytes to L-selectin on other leukocytes. The physiologic expression of the selectins is tightly controlled to limit the inflammatory response. But dysregulated expression of the selectins may contribute to inflammatory and thrombotic disorders, and perhaps to tumor metastases.