Binding of human neutrophils to cell-surface anchored Tamm-Horsfall glycoprotein in tubulointerstitial nephritis

Kidney Int. 1999 May;55(5):1787-99. doi: 10.1046/j.1523-1755.1999.00439.x.


Background: Human Tamm-Horsfall glycoprotein (T-H) is a glycosylphosphatidylinositol-anchored protein exposed at the surface of distal nephron cells, and urinary T-H is the released soluble counterpart. The latter has been implicated in tubulointerstitial nephritis, and the proinflammatory potential has been related to its ability to bind in vitro human neutrophils (PMNs). We have examined the conditions required for the binding of neutrophils to cell-surface anchored T-H and the consequent effects.

Methods: A HeLa cell-line derivative permanently transformed with human T-H cDNA and expressing T-H at the cell surface was used throughout the study. The adhesion of PMNs to cells expressing T-H was analyzed by immunofluorescence microscopy before and after the opsonization of cells with anti-T-H antibodies. The oxidative burst induced by adhesion of PMNs to the cells was determined by the activation of myeloperoxidase. Quantitative and qualitative changes in the release of T-H under the adhesion of activated PMNs were determined by dot-blot and Western blot analysis.

Results: No binding of neutrophils to cell-surface-anchored T-H was observed. On the contrary, the opsonization of cells with anti-T-H antibodies resulted in a dramatic adhesion of neutrophils. Such an adhesion induced the oxidative burst of PMNs and a large increment in the release of T-H, as well as the release of the slightly faster migrating T-H form, which is normally retained intracellularly.

Conclusions: These results support the notion that, after the autoimmune response, the adhesion of neutrophils to cell-surface T-H contributes to the pathogenesis of tubulointerstitial nephritis, favoring a further accumulation of T-H in the interstitium and inducing the loss of cell integrity via reactive oxygen metabolites generated by activated neutrophils.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / metabolism*
  • Autoantibodies / immunology
  • Binding, Competitive / immunology
  • Blotting, Western
  • Cell Adhesion / drug effects
  • Cell Adhesion / immunology
  • Fluorescent Antibody Technique
  • Gene Expression / immunology
  • Glycosylation
  • HeLa Cells
  • Humans
  • Mannose / metabolism
  • Mannose / pharmacology
  • Mucoproteins / genetics
  • Mucoproteins / immunology
  • Mucoproteins / urine*
  • N-Acetylneuraminic Acid / metabolism
  • Nephritis, Interstitial / immunology
  • Nephritis, Interstitial / metabolism*
  • Neutrophil Activation / immunology
  • Neutrophils / immunology
  • Neutrophils / metabolism*
  • Transfection
  • Tritium
  • Uromodulin
  • Wheat Germ Agglutinins / metabolism
  • Wheat Germ Agglutinins / pharmacology


  • Adjuvants, Immunologic
  • Autoantibodies
  • Mucoproteins
  • UMOD protein, human
  • Uromodulin
  • Wheat Germ Agglutinins
  • Tritium
  • N-Acetylneuraminic Acid
  • Mannose