Uromodulin (Tamm-Horsfall protein) is a leukocyte adhesion molecule

Uromodulin (Tamm-Horsfall protein), the most abundant constituent of human urine, is synthesized exclusively in the kidney tubular epithelium and its amino acid sequence suggests a capacity for cell adhesion. We investigated adhesion between human uromodulin and neutrophils by allowing uromodulin, immobilized on microtiter plates, to interact with neutrophils. It was found that neutrophils attached to uromodulin in a saturable manner. The binding was inhibited by uromodulin in solution. It required metabolically active cells, was calcium sensitive and could be inhibited by arginine-glycine- aspartate-containing peptides in solution. These data suggest that uromodoulin can act as a specific ligand for neutrophils. This interaction is potentially important in leukocyte trafficking in the kidney and in the pathogenesis of interstitial nephritis.