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A novel accessory molecule Trim59 involved in cytotoxicity of BCG-activated macrophages

Xiangfeng Zhao1, Qihui Liu, Baiqiu Du

  • 1Department of Immunology, Norman Bethune College of Medicine, Jilin University, Changchun, 130021, China. zxf184@163.com

Molecules and Cells
|September 6, 2012
PubMed

Insights

Trim59 is a membrane protein crucial for BCG-activated macrophage (BAM) tumoricidal activity. Blocking Trim59 significantly reduced BAM

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • BCG-activated macrophages (BAM) exhibit tumoricidal activity via cell-cell contact.
  • Membrane proteins play a vital role in macrophage-mediated cytotoxicity, but few have been identified.
  • Trim59 was identified as a surface molecule specifically expressed on BAM membranes.

Purpose of the Study:

  • To investigate the role of Trim59 in BAM-mediated tumor cell killing.
  • To characterize the expression pattern of Trim59.
  • To elucidate the function of Trim59 in macrophage activity.

Main Methods:

  • Cloning and prokaryotic expression of the extracellular domain of Trim59.
  • Purification of recombinant Trim59 protein and generation of polyclonal antibodies.
  • Immunohistochemistry to determine Trim59 expression in various tissues.
  • In vitro assays to assess the effect of Trim59 blockade on BAM cytotoxicity and macrophage phagocytosis.

Main Results:

  • Trim59 is abundantly expressed in spleen, stomach, and ovary; intermediately in brain, lung, kidney, muscle, and intestine; and absent in thymus, liver, heart, and uterus.
  • Antibody-mediated blockade of Trim59 significantly reduced BAM cytotoxicity against MCA207 tumor cells.
  • Overexpression of Trim59 enhanced pinocytosis and phagocytosis in Raw264.7 cells, but did not directly lyse tumor cells.
  • Trim59 appears to be an accessory molecule mediating BAM tumoricidal functions and is correlated with phagocytosis.

Conclusions:

  • Trim59 is an indispensable molecule for maintaining the tumoricidal activity of BCG-activated macrophages.
  • Trim59 plays a role in mediating cell-molecule interactions, enhancing phagocytosis.
  • Trim59 is a significant contributor to macrophage-based anti-tumor functions.

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