Expression of functionally different dectin-1 isoforms by murine macrophages

Sigrid E M Heinsbroek, Philip R Taylor, Marcela Rosas, Janet Anne Willment, David L Williams, Siamon Gordon, Gordon D Brown

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77 Citations (Scopus)

Abstract

Dectin-1 is a specific receptor for beta-glucans and a major receptor for fungal particles on macrophages (Mphi). It is a type II membrane receptor that has a C-terminal, NK-like, C-type lectin-like domain separated from the cell membrane by a short stalk region and a cytoplasmic immunoreceptor tyrosine-based activation-like motif. We observed functional differences in dectin-1-dependent recognition of fungal particles by Mphi from different mouse strains. RT-PCR analysis revealed that mice have at least two splice forms of dectin-1, generated by differential usage of exon 3, encoding the full-length dectin-1A and a stalkless Mphi dectin-1B. Mphi from BALB/c mice and genetically related mice expressed both isoforms in similar amounts, whereas Mphi from C57BL/6 and related mice mainly expressed the smaller isoform. NIH-3T3 fibroblast and RAW264.7 macrophage cell lines stably expressing either isoform were able to bind and phagocytose zymosan at 37 degrees C. However, binding by the smaller dectin-1B isoform was significantly affected at lower temperatures. These properties were shared by the equivalent human isoforms. The relative ability of each of the isoforms to induce TNF-alpha production in RAW264.7 Mphi was also found to be different. These results are the first evidence that dectin-1 isoforms are functionally distinct and indicate that differential isoform usage may represent a mechanism of regulating cellular responses to beta-glucans.
Original languageEnglish
Pages (from-to)5513-5518
Number of pages6
JournalThe Journal of Immunology
Volume176
Issue number9
Publication statusPublished - 1 May 2006

Keywords

  • Animals
  • Cell Line
  • Gene Expression Regulation
  • Humans
  • Macrophages
  • Membrane Proteins
  • Mice
  • Nerve Tissue Proteins
  • Protein Isoforms
  • Temperature
  • Tumor Necrosis Factor-alpha
  • Zymosan

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  • Cite this

    Heinsbroek, S. E. M., Taylor, P. R., Rosas, M., Willment, J. A., Williams, D. L., Gordon, S., & Brown, G. D. (2006). Expression of functionally different dectin-1 isoforms by murine macrophages. The Journal of Immunology, 176(9), 5513-5518.