The Leukointegrin Alpha d/Beta₂ (αd/CD18): Specific Changes in Surface Expression in Patients on Hemodialysis

Alpha d/CD18 is a newly discovered leukocyte adhesion molecule with sequence homology to CD11a, b and c of the β₂ integrin family. Little is known about αd expression in vivo, particularly how it compares with the other β₂ integrins. Previous studies have demonstrated that β₂ integrin expression, particularly CD11b, is upregulated in vivo during hemodialysis (HD) with complement activating membranes. These changes may contribute to the immunologic abnormalities seen in HD patients. Given the well described changes of β₂ integrins in these patients, we hypothesized that ad expression could also be altered by HD. Using flow cytometry with two specific antibodies to αd, ad expression in healthy adults (n=16) was compared on macrophages (MO) > polymorphonuclear cells (PMNs) > lymphocytes (LY). Phorbol ester treatment of leukocytes in vitro significantly increased expression on MO and PMN, but not LY. Chronic HD patients at baseline (n = 15) had elevated (P < 0.05) αd mean channel fluorescence (MCF) on MOs, PMNs and LYs compared to normals. PMN ad MCF increased at 15min into HD, but then returned to baseline levels at 180min. Alpha d MCF for LYs decreased at 180min, while MOs levels were unchanged. Alpha d expression is increased in chronic renal failure and further regulated by hemodialysis, but with unique characteristics compared to the other β₂ integrins. Alpha d may be important in abnormal cell-cell contacts in renal failure.