MrgX2-mediated internalization of LL-37 and degranulation of human LAD2 mast cells

Taisuke Murakami, Kaori Suzuki, Francois Niyonsaba, Hiroyuki Tada, Johannes Reich, Hiroshi Tamura, Isao Nagaoka

研究成果: Article

3 引用 (Scopus)

抜粋

LL-37 is the sole antimicrobial peptide of human cathelicidin comprising 37 amino acids, which is expressed mainly in epithelial cells and neutrophils, and activates mast cells. In the present study, in order to elucidate the mechanism of mast cell activation by LL-37, the associations between the internalization of LL-37 and Mas-related gene X2 (MrgX2)-mediated mast cell activation (degranulation) was investigated using the human mast cell line, LAD2. LL-37 was rapidly internalized into the cells, and induced degranulation, as assessed by the extracellular release of β-hexosaminidase. Pertussis toxin, a G-protein inhibitor, significantly suppressed the internalization of LL-37 and the degranulation of LAD2 cells. Furthermore, small interfering (si)-RNA-mediated knockdown of MrgX2, a putative G protein-coupled receptor for LL-37, inhibited the internalization of LL-37 and degranulation of LAD2 cells. Notably, LL-37 internalization was enhanced by the stable expression of MrgX2 in HMC-1 and 293 cells. In addition, the internalized LL-37 mainly colocalized with MrgX2 in the perinuclear region of LAD2 cells. Furthermore, neuraminidase treatment, which removes negatively charged sialic acid from the cell surface, markedly reduced the internalization of LL-37 and degranulation of LAD2 cells, and clathrin-mediated endocytosis inhibitors (dynasore and chlorpromazine) inhibited the internalization and degranulation of LAD2 cells. Taken together, these observations indicated that LL-37 may bind the negatively charged cell surface molecules, rapidly internalize into the cells via clathrin-mediated endocytosis and interact with MrgX2 to activate mast cells (LAD2 cells).

元の言語English
ページ(範囲)4951-4959
ページ数9
ジャーナルMolecular medicine reports
18
発行部数6
DOI
出版物ステータスPublished - 2018 12

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Oncology
  • Cancer Research

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  • これを引用

    Murakami, T., Suzuki, K., Niyonsaba, F., Tada, H., Reich, J., Tamura, H., & Nagaoka, I. (2018). MrgX2-mediated internalization of LL-37 and degranulation of human LAD2 mast cells. Molecular medicine reports, 18(6), 4951-4959. https://doi.org/10.3892/mmr.2018.9532