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Cell-to-cell interaction is required to induce proteinuria in in situ immune complex glomerulonephritis

T Oda1, M Kimura, A Hishida

  • 1Department of Internal Medicine, Hamamatsu University School of Medicine, Japan.

The Journal of Laboratory and Clinical Medicine
|August 26, 1998
PubMed

Insights

Adhesion molecules like ICAM-1, LFA-1, and selectins are crucial for developing cationized antigen-induced immune complex glomerulonephritis (CAICGN). Targeting these molecules early prevents proteinuria, highlighting their role in early nephritis development.

Area of Science:

  • Nephrology
  • Immunology
  • Cell Biology

Background:

  • Cationized antigen-induced in situ immune complex glomerulonephritis (CAICGN) is a model for kidney inflammation.
  • The roles of specific adhesion molecules in CAICGN pathogenesis are not fully understood.

Purpose of the Study:

  • To investigate the involvement of intercellular adhesion molecule-1 (ICAM-1), lymphocyte function-associated antigen-1 (LFA-1), and selectins in CAICGN development.
  • To determine the therapeutic window for targeting these adhesion molecules.

Main Methods:

  • CAICGN was induced in rats by perfusing cationized human immunoglobulin G (CaIgG).
  • Animals were treated with monoclonal antibodies (mAbs) against ICAM-1 and LFA-1, or a sulfatide (selectin ligand).
  • Albuminuria, polymorphonuclear leukocyte (PMN) infiltration, and glomerular immunoreactant deposition were assessed.

Main Results:

  • Early treatment (within 2 days) with ICAM-1/LFA-1 mAbs or sulfatide completely suppressed proteinuria development.
  • Sulfatide attenuated early PMN infiltration, but ICAM-1/LFA-1 mAbs did not.
  • Late treatment (day 4 or 5) did not affect albuminuria, indicating a critical early therapeutic window.

Conclusions:

  • Adhesion molecules ICAM-1, LFA-1, and selectins are critical for the development of proteinuria in CAICGN.
  • The therapeutic effect of targeting these molecules is time-sensitive, effective only during the early phase of PMN infiltration.

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