The role of selectins in inflammation and disease.
Selectins are carbohydrate-binding molecules that bind to fucosylated and sialylated glycoprotein ligands, and are found on endothelial cells, leukocytes and platelets. They are involved in trafficking of cells of the innate immune system, T lymphocytes and platelets. An absence of selectins or selectin ligands has serious consequences in mice or humans, leading to recurrent bacterial infections and persistent disease. Selectins are involved in constitutive lymphocyte homing, and in chronic and acute inflammation processes, including post-ischemic inflammation in muscle, kidney and heart, skin inflammation, atherosclerosis, glomerulonephritis and lupus erythematosus. Selectin-neutralizing monoclonal antibodies, recombinant soluble P-selectin glycoprotein ligand 1 and small-molecule inhibitors of selectins have been tested in clinical trials on patients with multiple trauma, cardiac indications and pediatric asthma, respectively. Anti-selectin antibodies have also been successfully used in preclinical models to deliver imaging contrast agents and therapeutics to sites of inflammation. Further improvements in the efficiency, availability, specificity and pharmacokinetics of selectin inhibitors, and specialized application routes and schedules, hold promise for therapeutic indications.
Ley
Klaus
K
Cardiovascular Research Center, MR5 Building, Room 1013, University of Virginia, PO Box 801394, Charlottesville, VA 22908-1394, USA. klausley@virginia.edu
D000595:Amino Acid Sequence; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001249:Asthma / Q000628:therapy; D001792:Blood Platelets / Q000502:physiology; D002318:Cardiovascular Diseases / Q000628:therapy*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology*; D008024:Ligands; D051379:Mice; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology; D009104:Multiple Trauma / Q000628:therapy; D019087:Selectins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*
D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D008024:Ligands; D019087:Selectins