The functional relevance of the lectin-like activities of cytokines: TNF as an illustrative example

Mammalian cytokines modulate the activity of the immune system. It is generally accepted that the action of cytokines results from their binding to specific receptors. However, many cytokines were shown to contain two domains. The first domain defines indeed the receptor-binding site. The second domain localized at the opposite to the receptor-binding site is necessary for the expression of the full biological activity of the cytokine. However, the exact function of the latter domain remains largely unknown. Recent evidences have shown that second domain of cytokines displays lectin-like activity allowing interaction of the cytokines with glycosaminoglycans on the cell surface of mammalian cells, thereby resulting in modulation of their biological activities. In addition, it has been suggested that the lectin-like domains of cytokines represent pathogen-specific recognition sites that can contribute to their elimination. This review focuses on the physiological relevance of the lectin-like activity of cytokines during the innate immune response in mammals, using TNF as an illustrative example.