John H. Musser*, Mark B. Anderson and Daniel E. Levy Pages 221 - 232 ( 12 )
The selectins are a family of cell adhesion molecules involved in the rolling stage of the transendothelial migration of leukocytes and their principal interaction is with cell-surface carbohydrates such as sialyl Lewis X (sLex). The selectin family currently consists of E-selectin, found on cytokine-activated endothelial cells, L selectin, identified by reaction with the monoclonal antibody MEL-14, and P-selectin, characterized utilizing antibodies differentiating between activated and resting platelets. The structural motifs of the selectins consist of a lectin binding domain succeeded by an epidermal growth factor (EGF) region. The oligosaccharide, sLeX, binds to E-selectin while L- and P-selectin recognize sLex or Lex related carbohydrates via the lectin binding domain.
Since the extravasation of leukocytes is associated with disorders including immunoinflammatory diseases, reperfusion injury and adult respiratory distress syndrome, agents that block the initial process of leukocyte adhesion to the endothelium may have therapeutic utility.
The potential therapeutic agents based on selectin binding inhibition are either large molecules related to selectins such as protein receptors/chimeras, monoclonal antibodies or peptidic/peptidomimetic compounds, or ligand-based small molecules such as oligosaccharides or carbohydrate mimics (Glycomimetics).
An alternative approach to selectin-mediated leukocyte trafficking other than selectin binding inhibition involves the modulation of sLex biosynthesis via the inhibition of glycosyltransferases. Since sLex is an oligosaccharide, mimics of this selectin ligand may be thought of as a new class of glycomimetics.