DIFFERENTIALLY REGULATED CELL-SURFACE EXPRESSION OF LEUKOCYTE ADHESION RECEPTORS ON NEUTROPHILS

To elucidate the molecular mechanisms accounting for hemodialysis-induced neutropenia, the regulation of plasma membrane expression of leukocyte adhesion glycoproteins was investigated by both flow cytometry and immunoprecipitation techniques. The members of the LFA family of integrins, Mac-1/Mol (CD11/CD18) and gp150/95 (CD11c/CD18), involved in adhesion of myeloid cells to endothelia and other substrates, were found to be overexpressed on the plasma membrane of neutrophils from patients undergoing hemodialysis with a Cuprophane dialyzer, whereas no change was observed in the expression of LFA-1 (CD11a/CD18). By contrast, dialysis with Cuprophane membranes, as well as in vitro treatment with different activating agents, induced a downregulation on the expression of both the Leu-8/LAM-1 antigen, the human neutrophil peripheral lymph node homing receptor, and the CD43 major sialoglycoprotein involved in leukocyte homotypic adhesion. Kinetics studies showed that these up- and downregulatory processes of antigen expression occur very rapidly, correlating with maximal neutropenia. Recovery of initial levels of expression of CD11b/CD18 and Leu-8/LAM-1 adhesion molecules was observed after one hour of hemodialysis. However, the basal expression of CD43 was not restored by that time. The coordinated upregulation of CD11b and CD11c and downregulation of LAM-1 and CD43 adhesion receptors provide molecular mechanisms for understanding leukoaggregation, adherence to endothelia, and extravasation of neutrophils ultimately leading to the hemodialysis-induced neutropenia.