ORIGINAL RESEARCH ARTICLE
Front. Immunol., 12 August 2013 | doi: 10.3389/fimmu.2013.00230
Binding of soluble yeast β-glucan to human neutrophils and monocytes is complement-dependent
- Biothera, Eagan, MN, USA
The immunomodulatory properties of yeast β-1,3/1,6 glucans are mediated through their ability to be recognized by human innate immune cells. While several studies have investigated binding of opsonized and unopsonized particulate β-glucans to human immune cells mainly via complement receptor 3 (CR3) or Dectin-1, few have focused on understanding the binding characteristics of soluble β-glucans. Using a well-characterized, pharmaceutical-grade, soluble yeast β-glucan, this study evaluated and characterized the binding of soluble β-glucan to human neutrophils and monocytes. The results demonstrated that soluble β-glucan bound to both human neutrophils and monocytes in a concentration-dependent and receptor-specific manner. Antibodies blocking the CD11b and CD18 chains of CR3 significantly inhibited binding to both cell types, establishing CR3 as the key receptor recognizing the soluble β-glucan in these cells. Binding of soluble β-glucan to human neutrophils and monocytes required serum and was also dependent on incubation time and temperature, strongly suggesting that binding was complement-mediated. Indeed, binding was reduced in heat-inactivated serum, or in serum treated with methylamine or in serum reacted with the C3-specific inhibitor compstatin. Opsonization of soluble β-glucan was demonstrated by detection of iC3b, the complement opsonin on β-glucan-bound cells, as well as by the direct binding of iC3b to β-glucan in the absence of cells. Binding of β-glucan to cells was partially inhibited by blockade of the alternative pathway of complement, suggesting that the C3 activation amplification step mediated by this pathway also contributed to binding.
Keywords: C3, opsonization, CR3, β-glucans, neutrophils, monocytes
Citation: Bose N, Chan ASH, Guerrero F, Maristany CM, Qiu X, Walsh RM, Ertelt KE, Jonas AB, Gorden KB, Dudney CM, Wurst LR, Danielson ME, Elmasry N, Magee AS, Patchen ML and Vasilakos JP (2013) Binding of soluble yeast β-glucan to human neutrophils and monocytes is complement-dependent. Front. Immunol. 4:230. doi: 10.3389/fimmu.2013.00230
Received: 06 May 2013; Accepted: 22 July 2013;
Published online: 12 August 2013.
Published online: 12 August 2013.
Edited by:
Zvi Fishelson, Tel Aviv University, Israel
Reviewed by:
Anna M. Blom, Lund University, SwedenJoana Vitte, Aix Marseille Université, France
Zsuzsa Bajtay, Lorand Eotvos University, Hungary
Copyright: © 2013 Bose, Chan, Guerrero, Maristany, Qiu, Walsh, Ertelt, Jonas, Gorden, Dudney, Wurst, Danielson, Elmasry, Magee, Patchen and Vasilakos. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Nandita Bose, Biothera, 3388 Mike Collins Drive, Eagan, MN 55121, USA e-mail: nbose@biothera.com
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