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International Immunology Advance Access originally published online on October 11, 2006
International Immunology 2006 18(12):1663-1670; doi:10.1093/intimm/dxl100
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© The Japanese Society for Immunology. 2006. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

An invertebrate TNF functional analogue activates macrophages via lectin–saccharide interaction with ion channels

Martin Bilej1, Radka Josková1, Rafael Van den Bergh2, Petra Procházková1, Marcela Silerová1, Paul Ameloot3, Patrick De Baetselier2 and Alain Beschin2

1 Department of Immunology, Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídenská 1083, 142 20 Prague 4, Czech Republic
2 Laboratory of Cellular and Molecular Immunology, Department of Cellular and Molecular Interactions, ‘Vlaams Interuniversitair Instituut voor Biotechnologie, Vrije Universiteit Brussel', Brussels, Belgium
3 Department for Molecular Biomedical Research, ‘Vlaams Interuniversitair Instituut voor Biotechnologie’, Ghent, Belgium

Correspondence to: M. Bilej; E-mail: mbilej{at}biomed.cas.cz

The invertebrate pattern-recognition protein named coelomic cytolytic factor (CCF) and the mammalian cytokine tumor necrosis factor (TNF) share functional analogies that are based on a similar saccharide recognition specificity. In particular, CCF and TNF have been shown to interact with ion channels on the surface of vertebrate cells via N,N'-diacetylchitobiose lectin-like activity. In the present study, we show that CCF-induced membrane depolarization results in the release of TNF, IL-6 and nitric oxide (NO) by macrophages via nuclear factor-{kappa}B signaling. Interestingly, our data suggest that TNF contributes, through lectin–saccharide interaction, to the secretion of IL-6 and NO induced by CCF. This experimental non-physiological setting based on the interaction of an invertebrate defense lectin with vertebrate cells involved in the innate immune response may have highlighted an evolutionarily ancient mechanism of macrophage activation in vertebrates.

Keywords: invertebrate cytokine, membrane depolarization, NF-{kappa}B, pattern-recognition protein, TNF

Transmitting editor: A. Falus


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