Adhesion molecules--their role in health and disease

Adhesion molecules play a major role in the recruitment of neutrophils to the site of inflammation. Neutrophils' localization is dynamic and involves multiple steps. In each step a different family of adhesion molecules takes part. The rolling phase is mediated by the selectin family, the E-, L-, and P- selectins, and their ligand, sialyl Lewis X. The next step, the activation and firm adhesion of the neutrophils to the endothelium, is regulated by the integrin family and their ligand, the Ig superfamily. The final step of transendothelial migration is again mediated by these two families of adhesion molecules. Although many in vitro studies were able to show the role of these molecules, their real importance was demonstrated in rare disease states where one of the adhesion molecule was absent. Two adhesion molecule deficiencies were described, both characterized by recurrent infections, defect in wound healing, and marked leukocytosis. Leukocyte adhesion deficiency (LAD) I is caused by a defect in the beta subunit of the integrin molecule, whereas in LAD II, the ligand for the selectin, the sialyl Lewis X is markedly decreased. Further insight was also gained with the generation of strains of mice deficient in one or another adhesion molecules (knock-out mice) Exploiting current knowledge on adhesion molecules and their role in health and disease, several trials have been designed to assess the effect of blocking their activity in conditions associated with increased expression of various adhesion molecules.