The leukointegrin alpha d/beta 2 (alpha d/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 beta 2 integrin family. Little is known about alpha d expression in vivo, particularly how it compares with the other beta 2 integrins. Previous studies have demonstrated that beta 2 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 beta 2 integrins in these patients, we hypothesized that alpha d expression could also be altered by HD. Using flow cytometry with two specific antibodies to alpha d, alpha d 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) alpha d mean channel fluorescence (MCF) on MOs, PMNs and LYs compared to normals. PMN alpha d MCF increased at 15 min into HD, but then returned to baseline levels at 180 min. Alpha d MCF for LYs decreased at 180 min, 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 beta 2 integrins. Alpha d may be important in abnormal cell-cell contacts in renal failure.
Rabb
H
H
Department of Internal Medicine and Pathology, James A. Haley V.A. Hospital, Tampa, FL 33612, USA.
Agosti
S J
SJ
Hakala
S
S
Hoffman
P
P
Gallatin
W M
WM
Ramirez
G
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000911:Antibodies, Monoclonal; D018845:CD11 Antigens; D002448:Cell Adhesion / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D039001:Integrin alpha Chains; D016023:Integrins / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008875:Middle Aged; D010704:Phorbols / Q000494:pharmacology; D016024:Receptors, Cytoadhesin; D006435:Renal Dialysis; D051437:Renal Insufficiency / Q000378:metabolism / Q000628:therapy; D013997:Time Factors
D000911:Antibodies, Monoclonal; D018845:CD11 Antigens; C406812:ITGAD protein, human; D039001:Integrin alpha Chains; D016023:Integrins; D010704:Phorbols; D016024:Receptors, Cytoadhesin; C033085:phorbol