Dectin-1 is a major beta-glucan receptor on macrophages

Gordon D Brown, Philip R Taylor, Delyth M Reid, Janet A Willment, David L Williams, Luisa Martinez-Pomares, Simon Y C Wong, Siamon Gordon

Research output: Contribution to journalArticle

682 Citations (Scopus)

Abstract

Zymosan is a beta-glucan- and mannan-rich particle that is widely used as a cellular activator for examining the numerous responses effected by phagocytes. The macrophage mannose receptor (MR) and complement receptor 3 (CR3) have historically been considered the major macrophage lectins involved in the nonopsonic recognition of these yeast-derived particles. Using specific carbohydrate inhibitors, we show that a beta-glucan receptor, but not the MR, is a predominant receptor involved in this process. Furthermore, nonopsonic zymosan binding was unaffected by genetic CD11b deficiency or a blocking monoclonal antibody (mAb) against CR3, demonstrating that CR3 was not the beta-glucan receptor mediating this activity. To address the role of the recently described beta-glucan receptor, Dectin-1, we generated a novel anti-Dectin-1 mAb, 2A11. Using this mAb, we show here that Dectin-1 was almost exclusively responsible for the beta-glucan-dependent, nonopsonic recognition of zymosan by primary macro-phages. These findings define Dectin-1 as the leukocyte beta-glucan receptor, first described over 50 years ago, and resolves the long-standing controversy regarding the identity of this important molecule. Furthermore, these results identify Dectin-1 as a new target for examining the immunomodulatory properties of beta-glucans for therapeutic drug design.
Original languageEnglish
Pages (from-to)407-12
Number of pages6
JournalJournal of Experimental Medicine
Volume196
Issue number3
Publication statusPublished - 2002

Fingerprint

Macrophage-1 Antigen
Macrophages
beta-Glucans
Zymosan
Monoclonal Antibodies
Mannans
Blocking Antibodies
Drug Design
Phagocytes
Lectins
Bacteriophages
Leukocytes
Yeasts
Carbohydrates
dectin 1
beta-glucan receptor
mannose receptor
Therapeutics

Keywords

  • Animals
  • Glucans
  • Macrophage-1 Antigen
  • Macrophages
  • Membrane Proteins
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins
  • Receptors, Immunologic
  • Zymosan

Cite this

Brown, G. D., Taylor, P. R., Reid, D. M., Willment, J. A., Williams, D. L., Martinez-Pomares, L., ... Gordon, S. (2002). Dectin-1 is a major beta-glucan receptor on macrophages. Journal of Experimental Medicine, 196(3), 407-12.

Dectin-1 is a major beta-glucan receptor on macrophages. / Brown, Gordon D; Taylor, Philip R; Reid, Delyth M; Willment, Janet A; Williams, David L; Martinez-Pomares, Luisa; Wong, Simon Y C; Gordon, Siamon.

In: Journal of Experimental Medicine, Vol. 196, No. 3, 2002, p. 407-12.

Research output: Contribution to journalArticle

Brown, GD, Taylor, PR, Reid, DM, Willment, JA, Williams, DL, Martinez-Pomares, L, Wong, SYC & Gordon, S 2002, 'Dectin-1 is a major beta-glucan receptor on macrophages', Journal of Experimental Medicine, vol. 196, no. 3, pp. 407-12.
Brown GD, Taylor PR, Reid DM, Willment JA, Williams DL, Martinez-Pomares L et al. Dectin-1 is a major beta-glucan receptor on macrophages. Journal of Experimental Medicine. 2002;196(3):407-12.
Brown, Gordon D ; Taylor, Philip R ; Reid, Delyth M ; Willment, Janet A ; Williams, David L ; Martinez-Pomares, Luisa ; Wong, Simon Y C ; Gordon, Siamon. / Dectin-1 is a major beta-glucan receptor on macrophages. In: Journal of Experimental Medicine. 2002 ; Vol. 196, No. 3. pp. 407-12.
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