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

G. D. Brown, P. R. Taylor, D. M. Reid, J. A. Willment, D. Williams, L. Martinez-Pomares, Simon Yuk Chun Wong, S. Gordon

Research output: Contribution to journalArticle

668 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 m-Ab, we show here that Dectin-1 was almost exclusively responsible for the beta-glucan-dependent, nonopsonic recognition of zymosan by primary macrophages. 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)407-412
Number of pages5
JournalJournal of Experimental Medicine
Volume196
Issue number3
DOIs
Publication statusPublished - Aug 2002

Keywords

  • lectin
  • macrophage
  • receptor
  • immunology
  • glucans
  • ALTERNATIVE COMPLEMENT PATHWAY
  • MOUSE PERITONEAL-MACROPHAGES
  • BINDING LECTIN SITE
  • MURINE MACROPHAGES
  • HUMAN-MONOCYTES
  • CD11B/CD18
  • ZYMOSAN
  • PHAGOCYTOSIS
  • SPECIFICITY
  • LEUKOCYTES

Cite this

Brown, G. D., Taylor, P. R., Reid, D. M., Willment, J. A., Williams, D., Martinez-Pomares, L., ... Gordon, S. (2002). Dectin-1 is a major ß-glucan receptor on macrophages. Journal of Experimental Medicine, 196(3), 407-412. https://doi.org/10.1084/jem.20020470

Dectin-1 is a major ß-glucan receptor on macrophages. / Brown, G. D.; Taylor, P. R.; Reid, D. M.; Willment, J. A.; Williams, D.; Martinez-Pomares, L.; Wong, Simon Yuk Chun; Gordon, S.

In: Journal of Experimental Medicine, Vol. 196, No. 3, 08.2002, p. 407-412.

Research output: Contribution to journalArticle

Brown, GD, Taylor, PR, Reid, DM, Willment, JA, Williams, D, Martinez-Pomares, L, Wong, SYC & Gordon, S 2002, 'Dectin-1 is a major ß-glucan receptor on macrophages', Journal of Experimental Medicine, vol. 196, no. 3, pp. 407-412. https://doi.org/10.1084/jem.20020470
Brown GD, Taylor PR, Reid DM, Willment JA, Williams D, Martinez-Pomares L et al. Dectin-1 is a major ß-glucan receptor on macrophages. Journal of Experimental Medicine. 2002 Aug;196(3):407-412. https://doi.org/10.1084/jem.20020470
Brown, G. D. ; Taylor, P. R. ; Reid, D. M. ; Willment, J. A. ; Williams, D. ; Martinez-Pomares, L. ; Wong, Simon Yuk Chun ; Gordon, S. / Dectin-1 is a major ß-glucan receptor on macrophages. In: Journal of Experimental Medicine. 2002 ; Vol. 196, No. 3. pp. 407-412.
@article{260797e07c034df9997ea774785e0df9,
title = "Dectin-1 is a major {\ss}-glucan receptor on macrophages",
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 m-Ab, we show here that Dectin-1 was almost exclusively responsible for the beta-glucan-dependent, nonopsonic recognition of zymosan by primary macrophages. 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.",
keywords = "lectin, macrophage, receptor, immunology, glucans, ALTERNATIVE COMPLEMENT PATHWAY, MOUSE PERITONEAL-MACROPHAGES, BINDING LECTIN SITE, MURINE MACROPHAGES, HUMAN-MONOCYTES, CD11B/CD18, ZYMOSAN, PHAGOCYTOSIS, SPECIFICITY, LEUKOCYTES",
author = "Brown, {G. D.} and Taylor, {P. R.} and Reid, {D. M.} and Willment, {J. A.} and D. Williams and L. Martinez-Pomares and Wong, {Simon Yuk Chun} and S. Gordon",
year = "2002",
month = "8",
doi = "10.1084/jem.20020470",
language = "English",
volume = "196",
pages = "407--412",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "3",

}

TY - JOUR

T1 - Dectin-1 is a major ß-glucan receptor on macrophages

AU - Brown, G. D.

AU - Taylor, P. R.

AU - Reid, D. M.

AU - Willment, J. A.

AU - Williams, D.

AU - Martinez-Pomares, L.

AU - Wong, Simon Yuk Chun

AU - Gordon, S.

PY - 2002/8

Y1 - 2002/8

N2 - 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 m-Ab, we show here that Dectin-1 was almost exclusively responsible for the beta-glucan-dependent, nonopsonic recognition of zymosan by primary macrophages. 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.

AB - 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 m-Ab, we show here that Dectin-1 was almost exclusively responsible for the beta-glucan-dependent, nonopsonic recognition of zymosan by primary macrophages. 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.

KW - lectin

KW - macrophage

KW - receptor

KW - immunology

KW - glucans

KW - ALTERNATIVE COMPLEMENT PATHWAY

KW - MOUSE PERITONEAL-MACROPHAGES

KW - BINDING LECTIN SITE

KW - MURINE MACROPHAGES

KW - HUMAN-MONOCYTES

KW - CD11B/CD18

KW - ZYMOSAN

KW - PHAGOCYTOSIS

KW - SPECIFICITY

KW - LEUKOCYTES

U2 - 10.1084/jem.20020470

DO - 10.1084/jem.20020470

M3 - Article

VL - 196

SP - 407

EP - 412

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 3

ER -