Lectins: biological effects and pharmaceutical applications

Abstract

Under the title "Lectins - biological effects and pharmaceutical applications" we have gathered investigation projects that target the biological implications of the interactions between lectins and carbohydrates, with special emphasis on lectins involving ligands expressed on the cell surface. Because previous studies carried out by our research group revealed that lectin interactions have potential application in therapeutics (provided that they are suitably described from a molecular viewpoint), the current project also aims at characterizing and enabling the pharmaceutical use of some lectins, specially KM+ from Artocarpus integrifolia. The research projects have been divided into 5 thematic issues, all of them with well established aims, as summarized below: 1) the role of lectin-carbohydrate interactions in the activation and regulation of cell function: the interaction between lectins and suitable glycans on the surface of leukocytes may induce signaling, cell activation, migration, and cytokine secretion. All these events give evidence of the major biological impact of such interaction. The projects comprising this thematic issue aim at investigating the biological implications of the interaction between mammalian, parasite, and plant lectins with glycans on the surface of leukocytes, no matter whether they are neutrophils, mastocytes, macrophages, dendritic celIs, or T -regulator cells; 2) the role of lectin-carbohydrate interactions in the modulation of immunity to infections: our previous studies have shown that some lectins interfere with IL-12 production upon their interaction with glycans present on the surface of antigen presenting cells. Therefore, animaIs administered with lectin KM+ as well as galectin-3-deficient mice may have their pattern of resistance/susceptibility to infections by intracellular parasites modified. This may be attributed to changes in the pattern of cytokine secretion by the host cell. Apart from cytokine production, other mechanisms may also contribute to the observed biological responses. The projects comprising this thematic issue target the evaluation of the effect of various lectins on cytokine production, as well as the influence of lectins on infections by different pathogens. It is expected that the molecular description of such interactions will reveal unknown events about the parasite-host relationship, as well as cast light on the mechanisms responsible for these interactions. This shall help establish new vaccination and immunotherapeutic strategies; 3) lectins involved in tumorgenesis and antitumorgenesis: upon interaction with abnormal glycans on tumor cells, both endogen and exogen lectins may interfere with the biology of cancer cells, with implications in their proliferation, death, adhesion to the extracellular matrix, migration, and metathesis. The projects comprising this thematic issue have the objective of investigating the impact of the interaction between some lectins and tumor cells, in both in vitro and in vivo models. A second aim is the study of endogen lectin expression in human tumors; 4) pharmaceutical applications of lectins: investigations on the biological implications of lectin-carbohydrate interactions developed by our group in the last years have resulted in potential pharmaceutical applications of some of the lectins studied by us. The projects comprising this issue are attempts at systematic studies on the use of lectins as inducers of tissue regeneration, immunotherapeutic agents, vaccine constituents, or tools for the isolation of immunotherapeutic drugs for veterinary ends; 5) obtention of recombinant lectin in its native and truncated forms - evaluation of their biological activities and pharmaceutical applications: one of the greatest obstacles to the clinical use of lectins is the immunogenicity o these molecules. Lectin KM+ is a potential candidate for pharmaceutical applications. The projects comprising this issue consist in a multidisciplinary effort that will be put into the obtention of truncated forms of the lectin, or "mini KM+", which do not bear immunogenicity but keep the biological properties of the original lectin. The projects also involve proposals for the obtention of recombinant lectin, produced in bacterial lipopolysaccharide-free E. coli, which is a preparation suitable for pharmaceutical use. (AU)