Altered glycosylation of Tamm-Horsfall glycoprotein derived from renal allograft recipients leads to changes in its biological function

作者：Wu Tsai Hung; Hsieh Song Chou; Li Ko Jen; Wu Cheng Han; Yu Chia Li^*; Yang An Hang; Tsai Chang Youh

来源：Transplant Immunology, 2008, 18(3): 237-245.

DOI：10.1016/j.trim.2007.07.001

• NF-kappa B p52
• proinflammatory cytokine-binding activity
• renal allograft transplantation
• Tamm-Horsfall glycoprotein (THP)

Background: Human urinary Tamm-Horsfall glycoprotein (THP) is a pleotropic protein that binds different cytokines and stimulates various immunocompetent cells. It is unclear whether these important functions of THP are altered in renal transplant patients.
Methods: We purified THPs from normal individuals (N-THP) and renal transplant patients receiving potent immunosuppressants (R-THP). The carbohydrate (CHO) compositions of THPs were probed by lectin-blotting and lectin-binding ELISA. The functions of THP were assessed by immune cell-stimulation as well as C1q, IL-1 beta, IL-8 and TNF-alpha-binding assays. The roles of CHO moieties in THPs were analyzed using CHO-degrading enzyme digestion.
Results: Compared to that of N-THP, the binding capacity of R-THP to Maackia amurensis, Galanthus nivalis and Datura stamonium decreased, indicating that R-THP contained lesser amount of Sia alpha(2,3)Gal/GalNAC, mannose residues, and beta(1,4)GlcNAc, but not GlcNAc/branched mannose. The binding capacity of R-THP to complement C1q and tumor necrosis factor (TNF)-alpha was also decreased. The stimulating effect of R-THP on mononuclear cell (MNC) proliferation and polymorphonuclear neutrophil (PMN) phagocytosis was less potent than that of N-THP. We found that the defective MNC-stimulation by R-THP was due to impaired NF-kappa B p52 nuclear translocation. The cell-stimulating effects of N- and R-THP could be abolished by digesting them with CHO-degrading enzymes, beta-galactosidase and neuraminidase. Interestingly, a potent apoptosis-inducing effect of R-THP on MNC and PMN was noted.
Conclusions: R-THP is not only modified in glycosylation but bears an apoptosis-inducing capacity on MNC and PMN, leading to an impaired immune function in renal transplant patients.

• 出版日期2008-1