Uromodulin (Tamm-Horsfall Glycoprotein): A Renal Ligand for Lymphokines

The protein portion of the immunosuppressive glycoprotein uromodulin is identical to the Tamm-Horsfall urinary glycoprotein and is synthesized in the kidney. Evidence that the glycoproteins are the same is based on amino acid sequence identity, immunologic cross-reactivity, and tissue localization t...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1987-09, Vol.237 (4821), p.1479-1484
Main Authors: Hession, Catherine, Decker, Jean M., Sherblom, Anne P., Kumar, Satish, Yue, Cho C., Mattaliano, Robert J., Tizard, Richard, Kawashima, Eric, Schmeissner, Ursula, Heletky, Sheryl, Chow, E. Pingchang, Burne, Cynthia A., Shaw, Alan, Muchmore, Andrew V.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Amino acid sequencing
Amino acids
Analytical, structural and metabolic biochemistry
Antiserum
Base Sequence
Biochemistry
Biological and medical sciences
Cloning, Molecular
Complementary DNA
Enzyme-Linked Immunosorbent Assay
Fundamental and applied biological sciences. Psychology
Glycoproteins
Glycoproteins - metabolism
Humans
immunosuppression
Immunosuppressive agents
Interleukin-1 - metabolism
kidney
Kidney - metabolism
Kidneys
L cells
Ligands - metabolism
Lymphokines
Lymphokines - metabolism
man
Medical research
Mice
Molecular Weight
Mucoproteins - analysis
Mucoproteins - genetics
Nucleic acids
Nucleotide sequence
Proteins
Recombinant Proteins - metabolism
RNA, Messenger - analysis
T lymphocytes
Tamm-Horsfall glycoprotein
Tumor Necrosis Factor-alpha
Urine
Uromodulin
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Summary:The protein portion of the immunosuppressive glycoprotein uromodulin is identical to the Tamm-Horsfall urinary glycoprotein and is synthesized in the kidney. Evidence that the glycoproteins are the same is based on amino acid sequence identity, immunologic cross-reactivity, and tissue localization to the thick ascending limb of Henle's loop. Nucleic acid sequencing of clones for uromodulin isolated from a complementary DNA bank from human kidney predicts a protein 639 amino acids in length, including a 24-amino acid leader sequence and a cysteine-rich mature protein with eight potential glycosylation sites. Uromodulin and preparations of Tamm-Horsfall glycoprotein bind to recombinant murine interleukin-1 (rIL-1) and human rIL-1$\alpha $, rIL-1$\beta $, and recombinant tumor necrosis factor (rTNF). Uromodulin isolated from urine of pregnant women by lectin adherence is more immunosuppressive than material isolated by the original salt-precipitation protocol of Tamm and Horsfall. Immunohistologic studies demonstrate that rIL-1 and rTNF bind to the same area of the human kidney that binds to antiserum specific for uromodulin. Thus, uromodulin (Tamm-Horsfall glycoprotein) may function as a unique renal regulatory glycoprotein that specifically binds to and regulates the circulating activity of a number of potent cytokines, including IL-1 and TNF.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.3498215