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Tumor necrosis factor-α can induce Langhans-type multinucleated giant cell formation derived from myeloid dendritic

Kozo Yasui1, Masato Yashiro, Mitsuru Tsuge

  • 1Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. k-yasui@city-hosp.naka.hiroshima.jp

Microbiology and Immunology
|August 20, 2011
PubMed

Insights

Tumor Necrosis Factor-alpha (TNF-α) drives the formation of Langhans-type multinucleated giant cells (MGCs). Neutralizing this cytokine with antibodies blocks MGC creation, highlighting TNF-α

Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Multinucleated giant cells (MGCs), particularly Langhans-type, are characteristic of granulomatous diseases.
  • Tumor Necrosis Factor-alpha (TNF-α) is implicated in MGC formation, but the precise mechanism requires elucidation.

Purpose of the Study:

  • To investigate the role of TNF-α in the in vitro formation of human Langhans-type MGCs.
  • To determine the effect of TNF-neutralizing antibodies on MGC development.

Main Methods:

  • Human peripheral blood monocytes were isolated and differentiated into myeloid dendritic cells (DCs) using GM-CSF and IL-4.
  • Cells were subsequently cultured with TNF-α, with or without TNF-neutralizing antibodies or anti-TNF receptor II antibodies.

Main Results:

  • TNF-α induced the formation of Langhans-type MGCs.
  • The presence of a TNF-neutralizing antibody, but not an anti-TNF receptor II antibody, inhibited MGC formation.
  • TNF-α-induced activation of Rho and focal adhesion kinases may mediate cell assembly.

Conclusions:

  • TNF-α is a key cytokine driving the formation of Langhans-type MGCs.
  • Targeting TNF-α could be a therapeutic strategy in granulomatous diseases characterized by MGCs.
  • MGCs exhibit lower superoxide anion production compared to myeloid DCs.

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