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Immune complexes increase nitric oxide production by interferon-gamma- stimulated murine macrophage-like J774.16

N Mozaffarian1, J W Berman, A Casadevall

  • 1Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.

Journal of Leukocyte Biology
|April 1, 1995
PubMed

Insights

Immunoglobulin G (IgG) isotypes enhance nitric oxide production in macrophages when combined with specific antigens, particularly when interferon-gamma (IFN-gamma) is present. This suggests IgG plays a role in pathogen defense by boosting macrophage immune responses.

Area of Science:

  • Immunology
  • Cell Biology
  • Microbiology

Background:

  • Macrophages are key immune cells involved in pathogen clearance.
  • Nitric oxide (NO) is a critical mediator of macrophage antimicrobial activity.
  • Immune complexes (ICs) can modulate macrophage function.

Purpose of the Study:

  • To investigate the effect of immune complexes (ICs) on nitric oxide (NO) production by murine macrophages.
  • To determine the role of different immunoglobulin G (IgG) isotypes and interferon-gamma (IFN-gamma) in modulating NO synthesis.

Main Methods:

  • Murine macrophage-like J774.16 cells were cultured.
  • Cells were incubated with Cryptococcus neoformans capsular polysaccharide and specific monoclonal antibodies to form ICs.
  • Nitrite synthesis (a marker of NO production) was measured in the presence and absence of recombinant murine IFN-gamma.

Main Results:

  • IgG isotypes (IgG1, IgG2, IgG2b, IgG3) in ICs significantly increased nitrite levels in the presence of IFN-gamma.
  • IgM isotype ICs did not enhance nitrite production.
  • Enhanced nitrite production required Fc gamma receptor (FcγR) cross-linking, as antibody or antigen alone did not induce this effect.

Conclusions:

  • Specific IgG isotypes, when forming immune complexes, enhance macrophage nitric oxide production, particularly with IFN-gamma.
  • This enhanced NO production suggests a protective role for IgG isotypes against pathogens.
  • FcγR cross-linking is essential for IC-mediated modulation of macrophage NO synthesis.

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