Tamm-Horsfall urinary glycoprotein enhances monokine release and augments lymphocyte proliferation.
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.
Yu
C L
CL
Department of Medicine, Veterans General Hospital-Taipei, Taiwan, ROC.
Tsai
C Y
CY
Lin
W M
WM
Liao
T S
TS
Chen
H L
HL
Sun
K H
KH
Chen
K H
KH
D015703:Antigens, CD / Q000032:analysis; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D001665:Binding Sites; D005260:Female; D006681:HLA-D Antigens / Q000032:analysis; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D015846:Monokines / Q000378:metabolism*; D009088:Mucoproteins / Q000378:metabolism / Q000494:pharmacology*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000378:metabolism / Q000494:pharmacology*; D015375:Receptors, Interleukin-2 / Q000032:analysis; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D058949:Uromodulin
D015703:Antigens, CD; D006681:HLA-D Antigens; D015846:Monokines; D009088:Mucoproteins; D011257:Pregnancy Proteins; D015375:Receptors, Interleukin-2; C548612:UMOD protein, human; D058949:Uromodulin