Tamm-Horsfall urinary glycoprotein enhances monokine release and augments lymphocyte proliferation

Immunopharmacology. Nov-Dec 1993;26(3):249-58. doi: 10.1016/0162-3109(93)90041-n.

Abstract

Tamm-Horsfall glycoprotein (THG) purified from pregnancy urine was found to stimulate normal human mononuclear cell (MNC) proliferation at a concentration greater than 10 micrograms/ml. This stimulation was non-specific because the percentage of B and T cell subpopulations including CD20, CD3, CD4, CD8 and CD4/CD8 ratio was not changed by THG. THG not only bound to human mononuclear cells but depolarized the membrane potential, increased 22Na+ uptake and enhanced the expression of IL-2R and HLA-class II antigens on these cells. The concentrations of sIL-2R, sCD4 and sCD8 in the THG-stimulated MNC culture supernatants were significantly increased compared with control supernatants. In addition, overnight incubation of THG (5-50 micrograms/ml) with MNC dose-responsively enhanced the syntheses of IL-1 beta, IL-6 and TNF-alpha by monocytes, with a maximal effect at 25 micrograms/ml. This monokine releasing activity of THG could be neutralized by a specific antibody against THG. When monocytes/macrophages were depleted from mononuclear cells by incubating with lysosomotropic methyl ester of L-leucine, THG retained the capability of stimulating lymphocytes proliferation but to a lesser degree. These results suggest that urinary THG activates monocytes to synthesize large amount of monokines through its membrane effect. The released monokines subsequently stimulate lymphocytes expressing IL-2R and HLA-class II antigens and finally lead to cell proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / analysis
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • Binding Sites
  • Female
  • HLA-D Antigens / analysis
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Lymphocyte Activation / drug effects*
  • Membrane Potentials / drug effects
  • Monocytes / drug effects*
  • Monocytes / immunology
  • Monokines / metabolism*
  • Mucoproteins / metabolism
  • Mucoproteins / pharmacology*
  • Pregnancy
  • Pregnancy Proteins / metabolism
  • Pregnancy Proteins / pharmacology*
  • Receptors, Interleukin-2 / analysis
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • Uromodulin

Substances

  • Antigens, CD
  • HLA-D Antigens
  • Monokines
  • Mucoproteins
  • Pregnancy Proteins
  • Receptors, Interleukin-2
  • UMOD protein, human
  • Uromodulin