Zymosan is a β-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 β-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 β-glucan receptor mediating this activity. To address the role of the recently described β-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 β-glucan-dependent, nonopsonic recognition of zymosan by primary macrophages. These findings define Dectin-1 as the leukocyte β-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 β-glucans for therapeutic drug design.
Identifer | oai:union.ndltd.org:ETSU/oai:dc.etsu.edu:etsu-works-20180 |
Date | 05 August 2002 |
Creators | Brown, Gordon D., Taylor, Philip R., Reid, Delyth M., Willment, Janet A., Williams, David L., Martinez-Pomares, Luisa, Wong, Simon Y.C., Gordon, Siamon |
Publisher | Digital Commons @ East Tennessee State University |
Source Sets | East Tennessee State University |
Detected Language | English |
Type | text |
Source | ETSU Faculty Works |
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