INVIVO BEHAVIOR OF NEUTROPHILS FROM 2 PATIENTS WITH DISTINCT INHERITED LEUKOCYTE ADHESION DEFICIENCY SYNDROMES

The selectins and the beta2-integrins (CD11/CD18) mediate distinct adh esive interactions between neutrophils and endothelial cells. Selectin s are believed to initiate binding by mediating neutrophil rolling, wh ereas beta2-integrins are required for subsequent activation-induced f irm sticking and emigration. In vitro evidence suggests that two endot helial cell selectins, P- and E-selectin, can mediate rolling by bindi ng to the carbohydrate ligand sialyl-Lewis(x) (sLe(x)) on neutrophil s urface glycoconjugates. To test the relative contribution of selectins and beta2-integrins in vivo we used intravital microscopy to study th e behavior of neutrophils from two patients with distinct inherited le ukocyte adhesion deficiency syndromes. Neutrophils from a patient suff ering from CD18 deficiency showed normal rolling behavior but were inc apable of sticking or emigrating upon chemotactic stimulation. Neutrop hils from a second patient with a newly described adhesion deficiency had normal CD18 but did not express sLe(x). These neutrophils rolled p oorly and also failed to stick in venules under shear force. Under sta tic conditions, however, chemoattractant-induced sticking and emigrati on could be observed. This demonstrates that both selectin-carbohydrat e-mediated initiation of adhesion and subsequent activation-induced be ta2-integrin engagement are essential for the normal function of human neutrophils in vivo.