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Role of macrophage receptor with collagenous structure in innate immune tolerance

Jian Jing1, Ivana V Yang, Lucy Hui

  • 1Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|May 14, 2013
PubMed

Insights

Histone methylation regulates macrophage receptor with collagenous structure (MARCO) expression and phagocytosis in tolerant macrophages. This epigenetic modification is crucial for MARCO

Area of Science:

  • Immunology
  • Epigenetics
  • Cell Biology

Background:

  • Macrophages are crucial for host defense via phagocytosis.
  • Macrophage receptor with collagenous structure (MARCO) mediates opsonin-independent phagocytosis.
  • Tolerant macrophages exhibit increased MARCO expression and phagocytosis, but its regulation is unclear.

Purpose of the Study:

  • Investigate the role of MARCO in LPS/lipoteichoic acid-induced macrophage tolerance.
  • Elucidate the transcriptional regulation of MARCO in tolerant macrophages.
  • Determine the impact of histone methylation on MARCO expression and function.

Main Methods:

  • Utilized mouse bone marrow-derived macrophages (BMDM).
  • Induced macrophage tolerance using LPS or lipoteichoic acid.
  • Assessed MARCO expression (transcript and protein) and phagocytic activity.
  • Analyzed H3K4me3 modification at the MARCO promoter.
  • Inhibited methylation using 5-aza-2'-deoxycytidine.

Main Results:

  • Tolerized BMDM showed increased MARCO expression and phagocytosis.
  • H3K4me3 modification at the MARCO promoter was elevated in tolerized BMDM.
  • Blocking methylation reduced H3K4me3, MARCO expression, and phagocytosis.
  • Methylation inhibition did not affect the inflammatory component of innate immune tolerance.

Conclusions:

  • Histone methylation is critical for MARCO expression and phagocytosis in tolerized macrophages.
  • Epigenetic regulation of MARCO contributes to innate immune tolerance.
  • MARCO's role in tolerance is independent of the inflammatory response.

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