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Related Experiment Videos

Angiotensin II binding to human mononuclear cells.

M R Simon1, M T Kamlay, M Khan

  • 1Medical Service, Veterans Administration Medical Center, Allen Park, MI 48101.

Immunopharmacology and Immunotoxicology
|January 1, 1989
PubMed
Summary

Angiotensin II may regulate immune responses in granulomatous diseases. Despite not binding like a classical receptor, it influences monocyte function, suggesting an immunomodulatory role.

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Area of Science:

  • Immunology
  • Endocrinology
  • Cell Biology

Background:

  • Elevated serum angiotensin converting enzyme activity is observed in human granulomatous diseases.
  • Angiotensin II demonstrates immunomodulatory effects, suppressing thymidine incorporation and augmenting gamma interferon production in human mononuclear cells.

Purpose of the Study:

  • To investigate the binding of Angiotensin II to human peripheral blood mononuclear cells and the U-937 monocyte cell line.
  • To elucidate the mechanism of Angiotensin II interaction with immune cells in the context of granulomatous inflammation.

Main Methods:

  • Studied Angiotensin II binding to U-937 cells using radioligand assays.
  • Assessed competitive inhibition, reversibility, and molecular integrity of the bound radioligand.
  • Investigated the effect of temperature and metabolic inhibitors on binding, indicative of endocytosis.

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Main Results:

  • Observed low-level, saturable specific binding of Angiotensin II to U-937 cells (Kd = 3 x 10(-10) M).
  • Binding was poorly reversible and competitively inhibited, and the radioligand's integrity was compromised post-binding, failing classical receptor definition.
  • Binding decreased at low temperatures and with metabolic inhibitors, suggesting endocytosis.

Conclusions:

  • Classical cell surface receptors for Angiotensin II were not demonstrated on human mononuclear cells or U-937 cells.
  • Endocytosis is likely involved in Angiotensin II uptake by these cells.
  • Angiotensin II and its metabolites modulate monocyte cyclic AMP production, indicating an immunoregulatory function despite the absence of classical receptors.