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Title
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Tamm-Horsfall glycoprotein: biology and clinical relevance.
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Authors
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F.Serafini-Cessi,
N.Malagolini,
D.Cavallone.
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Ref.
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Am J Kidney Dis, 2003,
42,
658-676.
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PubMed id
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Abstract
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Tamm-Horsfall glycoprotein (THP) is the most abundant urinary protein in
mammals. Urinary excretion occurs by proteolytic cleavage of the large
ectodomain of the glycosyl phosphatidylinositol-anchored counterpart exposed at
the luminal cell surface of the thick ascending limb of Henle's loop. We
describe the physical-chemical structure of human THP and its biosynthesis and
interaction with other proteins and leukocytes. The clinical relevance of THP
reported here includes: (1) involvement in the pathogenesis of cast nephropathy,
urolithiasis, and tubulointerstitial nephritis; (2) abnormalities in urinary
excretion in renal diseases; and (3) the recent finding that familial juvenile
hyperuricemic nephropathy and autosomal dominant medullary cystic kidney disease
2 arise from mutations of the THP gene. We critically examine the literature on
the physiological role and mechanism(s) that promote urinary excretion of THP.
Some lines of research deal with the in vitro immunoregulatory activity of THP,
termed uromodulin when isolated from urine of pregnant women. However, an
immunoregulatory function in vivo has not yet been established. In the most
recent literature, there is renewed interest in the capacity of urinary THP to
compete efficiently with urothelial cell receptors, such as uroplakins, in
adhering to type 1 fimbriated Escherichia coli. This property supports the
notion that abundant THP excretion in urine is promoted in the host by selective
pressure to obtain an efficient defense against urinary tract infections caused
by uropathogenic bacteria.
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