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Acemannan, a beta-(1,4)-acetylated mannan, induces nitric oxide production in macrophage cell line RAW 264.7

L Ramamoorthy1, M C Kemp, I R Tizard

  • 1Department of Veterinary Pathobiology, Texas A & M University, College Station 77843, USA. IOr7859@rigel.tamu.edu

Molecular Pharmacology
|October 1, 1996
PubMed

Insights

Acemannan, an antiviral immunomodulator, activates macrophages by increasing nitric oxide (NO) synthesis. This process involves the transcriptional induction of NO synthase, mediated by nuclear factor-kappa B signaling pathways.

Area of Science:

  • Immunology
  • Molecular Biology
  • Pharmacology

Background:

  • Acemannan is a beta-(1,4)-linked acetylated mannan with known antiviral properties.
  • It functions as an immunomodulator, demonstrating macrophage activation in prior studies.
  • Inducible nitric oxide synthase (iNOS) mediates macrophage cytotoxicity via transcriptional induction.

Purpose of the Study:

  • To investigate the mechanism by which acemannan activates macrophages.
  • To determine the role of nitric oxide (NO) synthesis in acemannan-induced macrophage activation.
  • To elucidate the transcriptional regulation of inducible NO synthase (iNOS) by acemannan.

Main Methods:

  • RAW 264.7 cells were treated with acemannan and interferon-gamma.
  • Nitric oxide (NO) synthesis was measured.
  • Messenger RNA (mRNA) expression for inducible NO synthase (iNOS) was assessed.
  • Nuclear factor-kappa B (NF-κB) involvement was evaluated using pyrrolidine dithiocarbamate inhibition.

Main Results:

  • Acemannan significantly increased NO synthesis in RAW 264.7 cells, particularly when combined with interferon-gamma.
  • This increase in NO production was correlated with elevated mRNA expression of iNOS.
  • Inhibition of NF-κB activation by pyrrolidine dithiocarbamate blocked the acemannan-induced NO synthesis.
  • These findings indicate that acemannan enhances macrophage activation through transcriptional upregulation of iNOS.

Conclusions:

  • Acemannan activates macrophages by upregulating the transcription of inducible NO synthase (iNOS).
  • The nuclear factor-kappa B (NF-κB) pathway plays a crucial role in mediating acemannan's effect on iNOS expression.
  • Acemannan's immunomodulatory and antiviral properties may be linked to its ability to enhance NO production via transcriptional control.

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