Skip to main content
NCBI home page
Immunology logoLink to Immunology
. 1993 Jun;79(2):203–210.

The interaction of Tamm-Horsfall protein with the extracellular matrix.

C Lambert 1, R Brealey 1, J Steele 1, G A Rook 1
PMCID: PMC1421872  PMID: 8344699

Abstract

Tamm-Horsfall protein (THP) is the major glycoprotein component of urine, yet its biological role remains obscure. Recent reports have suggested that a concanavalin A (Con A)-binding fraction of THP from pregnancy urine can bind the cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1). In order to investigate this claim in relation to THP from normal adult urine we raised monoclonal antibodies to THP and sought THP/TNF-alpha interactions in three separate assay systems. We found no evidence that THP binds to TNF-alpha under physiological conditions, but we observed that it exerts a weak, probably not physiologically relevant, but reproducible inhibitory effect on the toxicity of TNF-alpha for monolayers of L929 cells, even when the cells are pretreated with the THP, and washed before addition of the cytokine. Since our preparations of THP do not interact directly with TNF-alpha we postulated an interaction with the cells themselves, or with their extracellular matrix. The THP was found by ELISA, immunoblotting and immunohistology, to bind to as yet unidentified components of the extracellular matrix in a manner dependent on cations, pH and carbohydrates. These data, considered in the light of the published amino acid sequence and biochemical properties, suggest that THP is a member of a structural glycoprotein family known to modulate cell adhesion.

Full text

PDF
203

Images in this article

207Figure 4
on p.207
208Figure 5
on p.208

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abou-Zeid C., Smith I., Grange J. M., Ratliff T. L., Steele J., Rook G. A. The secreted antigens of Mycobacterium tuberculosis and their relationship to those recognized by the available antibodies. J Gen Microbiol. 1988 Feb;134(2):531–538. doi: 10.1099/00221287-134-2-531. [DOI] [PubMed] [Google Scholar]
  2. Bevilacqua M. P., Stengelin S., Gimbrone M. A., Jr, Seed B. Endothelial leukocyte adhesion molecule 1: an inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science. 1989 Mar 3;243(4895):1160–1165. doi: 10.1126/science.2466335. [DOI] [PubMed] [Google Scholar]
  3. Brown K. M., Muchmore A. V., Rosenstreich D. L. Uromodulin, an immunosuppressive protein derived from pregnancy urine, is an inhibitor of interleukin 1. Proc Natl Acad Sci U S A. 1986 Dec;83(23):9119–9123. doi: 10.1073/pnas.83.23.9119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Drickamer K. Membrane receptors that mediate glycoprotein endocytosis: structure and biosynthesis. Kidney Int Suppl. 1987 Dec;23:S167–S183. [PubMed] [Google Scholar]
  5. Fukuoka S., Freedman S. D., Yu H., Sukhatme V. P., Scheele G. A. GP-2/THP gene family encodes self-binding glycosylphosphatidylinositol-anchored proteins in apical secretory compartments of pancreas and kidney. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1189–1193. doi: 10.1073/pnas.89.4.1189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Heremans A., Cassiman J. J., Van den Berghe H., David G. Heparan sulfate proteoglycan from the extracellular matrix of human lung fibroblasts. Isolation, purification, and core protein characterization. J Biol Chem. 1988 Apr 5;263(10):4731–4739. [PubMed] [Google Scholar]
  7. Hession C., Decker J. M., Sherblom A. P., Kumar S., Yue C. C., Mattaliano R. J., Tizard R., Kawashima E., Schmeissner U., Heletky S. Uromodulin (Tamm-Horsfall glycoprotein): a renal ligand for lymphokines. Science. 1987 Sep 18;237(4821):1479–1484. doi: 10.1126/science.3498215. [DOI] [PubMed] [Google Scholar]
  8. Horton J. K., Davies M., Topley N., Thomas D., Williams J. D. Activation of the inflammatory response of neutrophils by Tamm-Horsfall glycoprotein. Kidney Int. 1990 Feb;37(2):717–726. doi: 10.1038/ki.1990.38. [DOI] [PubMed] [Google Scholar]
  9. Kumar S., Muchmore A. Tamm-Horsfall protein--uromodulin (1950-1990). Kidney Int. 1990 Jun;37(6):1395–1401. doi: 10.1038/ki.1990.128. [DOI] [PubMed] [Google Scholar]
  10. Lasky L. A., Singer M. S., Yednock T. A., Dowbenko D., Fennie C., Rodriguez H., Nguyen T., Stachel S., Rosen S. D. Cloning of a lymphocyte homing receptor reveals a lectin domain. Cell. 1989 Mar 24;56(6):1045–1055. doi: 10.1016/0092-8674(89)90637-5. [DOI] [PubMed] [Google Scholar]
  11. Meager A., Parti S., Leung H., Peil E., Mahon B. Preparation and characterization of monoclonal antibodies directed against antigenic determinants of recombinant human tumour necrosis factor (rTNF). Hybridoma. 1987 Jun;6(3):305–311. doi: 10.1089/hyb.1987.6.305. [DOI] [PubMed] [Google Scholar]
  12. Moonen P., Gaffner R., Wingfield P. Native cytokines do not bind to uromodulin (Tamm-Horsfall glycoprotein). FEBS Lett. 1988 Jan 4;226(2):314–318. doi: 10.1016/0014-5793(88)81446-7. [DOI] [PubMed] [Google Scholar]
  13. Muchmore A. V., Decker J. M. Uromodulin. An immunosuppressive 85-kilodalton glycoprotein isolated from human pregnancy urine is a high affinity ligand for recombinant interleukin 1 alpha. J Biol Chem. 1986 Oct 15;261(29):13404–13407. [PubMed] [Google Scholar]
  14. Neale M. L., Fiera R. A., Matthews N. Tumour cells which develop resistance to cytolysis by tumour necrosis factor have a different glycoform of a 105-kDa glycoprotein and lose the capacity to invade and metastasize. Int J Cancer. 1990 Jan 15;45(1):203–208. doi: 10.1002/ijc.2910450136. [DOI] [PubMed] [Google Scholar]
  15. O'Hanley P., Lark D., Falkow S., Schoolnik G. Molecular basis of Escherichia coli colonization of the upper urinary tract in BALB/c mice. Gal-Gal pili immunization prevents Escherichia coli pyelonephritis in the BALB/c mouse model of human pyelonephritis. J Clin Invest. 1985 Feb;75(2):347–360. doi: 10.1172/JCI111707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Orskov I., Ferencz A., Orskov F. Tamm-Horsfall protein or uromucoid is the normal urinary slime that traps type 1 fimbriated Escherichia coli. Lancet. 1980 Apr 19;1(8173):887–887. doi: 10.1016/s0140-6736(80)91396-3. [DOI] [PubMed] [Google Scholar]
  17. Pennica D., Kohr W. J., Kuang W. J., Glaister D., Aggarwal B. B., Chen E. Y., Goeddel D. V. Identification of human uromodulin as the Tamm-Horsfall urinary glycoprotein. Science. 1987 Apr 3;236(4797):83–88. doi: 10.1126/science.3453112. [DOI] [PubMed] [Google Scholar]
  18. Pytela R., Pierschbacher M. D., Ruoslahti E. A 125/115-kDa cell surface receptor specific for vitronectin interacts with the arginine-glycine-aspartic acid adhesion sequence derived from fibronectin. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5766–5770. doi: 10.1073/pnas.82.17.5766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ronco P., Brunisholz M., Geniteau-Legendre M., Chatelet F., Verroust P., Richet G. Physiopathologic aspects of Tamm-Horsfall protein: a phylogenetically conserved marker of the thick ascending limb of Henle's loop. Adv Nephrol Necker Hosp. 1987;16:231–249. [PubMed] [Google Scholar]
  20. Rook G. A., Steele J., Rademacher T. A monoclonal antibody raised by immunising mice with group A streptococci binds to agalactosyl IgG from rheumatoid arthritis. Ann Rheum Dis. 1988 Mar;47(3):247–250. doi: 10.1136/ard.47.3.247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ruoslahti E., Pierschbacher M. D. New perspectives in cell adhesion: RGD and integrins. Science. 1987 Oct 23;238(4826):491–497. doi: 10.1126/science.2821619. [DOI] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES