PMID- 18047931
OWN - NLM
STAT- MEDLINE
DCOM- 20080225
LR  - 20231213
IS  - 0966-3274 (Print)
IS  - 0966-3274 (Linking)
VI  - 18
IP  - 3
DP  - 2008 Jan
TI  - Altered glycosylation of Tamm-Horsfall glycoprotein derived from renal allograft 
      recipients leads to changes in its biological function.
PG  - 237-45
AB  - 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-1beta, 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 Siaalpha(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-kappaB 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.
FAU - Wu, Tsai-Hung
AU  - Wu TH
AD  - Division of Nephrology, Taipei Veterans General Hospital, and Institute of 
      Clinical Medicine, National Yang-Ming University, Taiwan.
FAU - Hsieh, Song-Chou
AU  - Hsieh SC
FAU - Li, Ko-Jen
AU  - Li KJ
FAU - Wu, Cheng-Han
AU  - Wu CH
FAU - Yu, Chia-Li
AU  - Yu CL
FAU - Yang, An-Hang
AU  - Yang AH
FAU - Tsai, Chang-Youh
AU  - Tsai CY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070801
PL  - Netherlands
TA  - Transpl Immunol
JT  - Transplant immunology
JID - 9309923
RN  - 0 (Cytokines)
RN  - 0 (Lectins)
RN  - 0 (Mucoproteins)
RN  - 0 (UMOD protein, human)
RN  - 0 (Uromodulin)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Apoptosis
MH  - Cytokines/metabolism
MH  - Female
MH  - Glycosylation
MH  - Humans
MH  - Kidney Transplantation/*immunology
MH  - Lectins/metabolism
MH  - Leukocytes, Mononuclear/cytology/immunology/metabolism
MH  - Male
MH  - Middle Aged
MH  - Mucoproteins/chemistry/immunology/*metabolism
MH  - Neutrophils/immunology/metabolism
MH  - Phagocytosis
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Uromodulin
MH  - NF-kappaB-Inducing Kinase
EDAT- 2007/12/01 09:00
MHDA- 2008/02/26 09:00
CRDT- 2007/12/01 09:00
PHST- 2007/02/27 00:00 [received]
PHST- 2007/07/08 00:00 [revised]
PHST- 2007/07/11 00:00 [accepted]
PHST- 2007/12/01 09:00 [pubmed]
PHST- 2008/02/26 09:00 [medline]
PHST- 2007/12/01 09:00 [entrez]
AID - S0966-3274(07)00141-4 [pii]
AID - 10.1016/j.trim.2007.07.001 [doi]
PST - ppublish
SO  - Transpl Immunol. 2008 Jan;18(3):237-45. doi: 10.1016/j.trim.2007.07.001. Epub 
      2007 Aug 1.