Selectins are a family of three cell adhesion molecules (L-, E-, and P-sele
ctin) specialized in capturing leukocytes from the bloodstream to the blood
vessel wall. This initial cell contact is followed by the selectin-mediate
d rolling of leukocytes on the endothelial cell surface. This represents th
e first step in a cascade of molecular interactions that lead to leukocyte
extravasation, enabling the processes of lymphocyte recirculation and leuko
cyte migration into inflamed tissue. The central importance of the selectin
s in these processes has been well documented in vivo by the use of adhesio
n-blocking antibodies as well as by studies on selectin gene-deficient mice
. This review focuses on the molecular mechanisms that regulate expression
and function(s) of the selectins and their ligands. Cell-surface expression
of the selectins is regulated by a variety of different mechanisms. The se
lectins bind to carbohydrate structures on glycoproteins, glycolipids, and
proteoglycans. Glycoproteins are the most likely candidates for physiologic
ally relevant ligands. Only a few glycoproteins are appropriately glycosyla
ted to allow strong binding to the selectins. Recently, more knowledge abou
t the structure and the regulated expression of some of the carbohydrates o
n these Ligands necessary for selectin binding has been accumulated. For at
least one of these Ligands, the physiological function is now well establi
shed. A novel and exciting aspect is the signaling function of the selectin
s and their ligands. Especially in the last two years, convincing data have
been published supporting the idea that selectins and glycoprotein ligands
of the selectins participate in the activation of leukocyte integrins.