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Simultaneous Study of the Recruitment of Monocyte Subpopulations Under Flow In Vitro
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Involvement of ADAM9 in multinucleated giant cell formation of blood monocytes

K Namba1, M Nishio, K Mori

  • 1Department of Microbiology, Mie University School of Medicine, 2-174, Edobashi, Tsu-Shi, Mie Prefecture, 514-8507, Japan.

Cellular Immunology
|February 8, 2002
PubMed

Insights

Researchers identified ADAM9 as a key protein involved in monocyte fusion, a process crucial for forming multinucleated giant cells like osteoclasts. This finding sheds light on monocyte-macrophage differentiation and potential therapeutic targets.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Monocytes differentiate into multinucleated giant cells, including osteoclasts, through cell fusion.
  • The specific fusion peptides mediating this process in monocytes remain largely unidentified.
  • ADAM proteins are transmembrane glycoproteins with diverse biological roles, including potential involvement in cell fusion.

Purpose of the Study:

  • To investigate which ADAM family members are expressed in monocytes upon stimulation.
  • To identify the specific ADAM protein functioning as a fusion factor in monocytes.
  • To elucidate the role of ADAM9 in CD98- and RANKL-mediated monocyte fusion.

Main Methods:

  • Quantitative analysis of ADAM mRNA expression in human blood monocytes.
  • Stimulation of monocytes with anti-CD98 antibody and RANKL + M-CSF.
  • Assessment of cell aggregation and multinucleated giant cell formation.
  • Inhibition studies using anti-ADAM9 antibody and a metalloprotease inhibitor (SI-27).

Main Results:

  • ADAM1, 8, 10, 12, 15, 17, 20, and 21 mRNAs were detected in monocytes.
  • ADAM9 and ADAM10 mRNA expression was significantly enhanced by anti-CD98 antibody and RANKL + M-CSF.
  • Anti-ADAM9 antibody blocked CD98- and RANKL-mediated cell fusion, while SI-27 also suppressed fusion.
  • ADAM9 expression is dependent on new protein synthesis and inhibited by genistein.

Conclusions:

  • ADAM9 is specifically expressed and functionally involved in CD98- and RANKL-mediated monocyte fusion.
  • ADAM9 is a strong candidate for a fusion peptide in blood monocytes.
  • This study provides novel insights into the molecular mechanisms of monocyte fusion and osteoclastogenesis.

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