Adhesion molecule deficiencies and their clinical significance.

Abstract

Adhesion molecules play a major role in the recruitment of neutrophils to the site of inflammation. Currently, two congenital hereditary Leukocyte Adhesion Deficiency (LAD) syndromes are recognized. LAD I is due to the absence of the beta subunit of the integrin molecule, while LAD II is caused by a deficiency of Sialy1 Lewis X, the neutrophil ligand for selectins. Clinically, both syndromes are characterized by recurrent bacterial infections, more severe in LAD I. Developmental abnormalities (growth and mental retardation) constitute a prominent feature of LAD II and may be attributed to a general defect found in fucose metabolism in LAD II. Neutrophil motility was found to be defective in both syndromes. Using activated umbilical endothelial cells, we showed that LAD I neutrophil do not bind to cells expressing ICAM-1, while LAD II cells do not bind to endothelial cells expressing E- or P-selectin. Skin window technique showed a marked decrease in margination in both syndromes. Using intravital microscopy we were able to show that the basic defect in LAD II is in the "rolling" phase, while in LAD I, firm adhesion and transmigration are defective. Studies of these two rare conditions emphasized the important in vivo roles of adhesion molecules in host defense mechanism.