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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)

Articles published in Agência FAPESP Newsletter about the research grant:
Experimental therapy with lectin is capable of stimulating the immune system 
Pesquisadores testam proteína capaz de estimular o sistema imunológico 

Scientific publications (20)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
BURANELLO, PATRICIA A. A.; BARBOSA-LORENZI, VALERIA C.; PINTO, MARCELO R.; PEREIRA-DA-SILVA, GABRIELA; BARREIRA, MARIA CRISTINA R. A.; JAMUR, MARIA CELIA; OLIVER, CONSTANCE. The lectin ArtinM activates RBL-2H3 mast cells without inducing degranulation. PLoS One, v. 15, n. 3 MAR 24 2020. Web of Science Citations: 0.
KIM, YEON JUNG; DE MOLON, RAFAEL SCAF; DA SILVA, VANESSA CAMILA; VEIGA CONRADO, MARINA CAVALCANTI ALBUQUERQUE; SPOLIDORIO, LUIS CARLOS; ANTUNES ROQUE-BARREIRA, MARIA CRISTINA; CIRELLI, JONI AUGUSTO. Topical application of lectin Artin M improves wound healing in defects created in the palatal mucosa: an in vivo study in dogs. ODONTOLOGY, FEB 2020. Web of Science Citations: 0.
OLIVEIRA, ALINE FERREIRA; FERNANDES, FABRICIO FREITAS; MARIANO, VANIA SAMMARTINO; ALMEIDA, FAUSTO; RUAS, LUCIANA PEREIRA; OLIVEIRA, LEANDRO LICURSI; OLIVER, CONSTANCE; JAMUR, MARIA CELIA; ROQUE-BARREIRA, MARIA CRISTINA. Paracoccin distribution supports its role in Paracoccidioides brasiliensis growth and dimorphic transformation. PLoS One, v. 12, n. 8 AUG 28 2017. Web of Science Citations: 1.
DA SILVA, THIAGO APARECIDO; MARTINS OLIVEIRA-BRITO, PATRICIA KELLEN; GONCALVES, THIAGO ELEUTERIO; VENDRUSCOLO, PATRICIA EDIVANIA; ROQUE-BARREIRA, MARIA CRISTINA. ArtinM Mediates Murine T Cell Activation and Induces Cell Death in Jurkat Human Leukemic T Cells. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 18, n. 7 JUL 2017. Web of Science Citations: 5.
DA SILVA, THIAGO APARECIDO; FERNANDES, FABRICIO FREITAS; ROQUE-BARREIRA, MARIA CRISTINA. Data on IL-17 production induced by plant lectins. DATA IN BRIEF, v. 7, p. 1584-1587, JUN 2016. Web of Science Citations: 3.
DA SILVA, THIAGO APARECIDO; MARIANO, VANIA SAMMARTINO; SARDINHA-SILVA, ALINE; DE SOUZA, MARIA APARECIDA; PATRIARCA MINEO, TIAGO WILSON; ROQUE-BARREIRA, MARIA CRISTINA. IL-17 Induction by ArtinM is Due to Stimulation of IL-23 and IL-1 Release and/or Interaction with CD3 in CD4(+) T Cells. PLoS One, v. 11, n. 2 FEB 22 2016. Web of Science Citations: 6.
ASSIS-MARQUES, MARIANA APRIGIO; OLIVEIRA, ALINE FERREIRA; RUAS, LUCIANA PEREIRA; DOS REIS, THAILA FERNANDA; ROQUE-BARREIRA, MARIA CRISTINA; RODRIGUES COELHO, PAULO SERGIO. Saccharomyces cerevisiae Expressing Gp43 Protects Mice against Paracoccidioides brasiliensis Infection. PLoS One, v. 10, n. 3 MAR 19 2015. Web of Science Citations: 12.
DA SILVA, THIAGO APARECIDO; DE SOUZA, MARIA APARECIDA; CECILIO, NERRY TATIANA; ROQUE-BARREIRA, MARIA CRISTINA. Activation of spleen cells by ArtinM may account for its immunomodulatory properties. Cell and Tissue Research, v. 357, n. 3, p. 719-730, SEP 2014. Web of Science Citations: 13.
MARIANO, VANIA SAMMARTINO; ZORZETTO-FERNANDES, ANDRE LUIZ; DA SILVA, THIAGO APARECIDO; RUAS, LUCIANA PEREIRA; NOHARA, LILIAN L.; DE ALMEIDA, IGOR CORREIA; ROQUE-BARREIRA, MARIA CRISTINA. Recognition of TLR2 N-Glycans: Critical Role in ArtinM Immunomodulatory Activity. PLoS One, v. 9, n. 6 JUN 3 2014. Web of Science Citations: 15.
DOS REIS ALMEIDA, FAUSTO BRUNO; PIGOSSO, LAURINE LACERDA; DE LIMA DAMASIO, ANDRE RICARDO; MONTEIRO, VALDIRENE NEVES; DE ALMEIDA SOARES, CELIA MARIA; SILVA, ROBERTO NASCIMENTO; ROQUE-BARREIRA, MARIA CRISTINA. alpha-(1,4)-Amylase, but not alpha- and beta-(1,3)-glucanases, may be responsible for the impaired growth and morphogenesis of Paracoccidioides brasiliensis induced by N-glycosylation inhibition. YEAST, v. 31, n. 1, p. 1-11, JAN 2014. Web of Science Citations: 7.
SOUZA, MARIA A.; CARVALHO, FERNANDA C.; RUAS, LUCIANA P.; RICCI-AZEVEDO, RAFAEL; ROQUE-BARREIRA, MARIA CRISTINA. The immunomodulatory effect of plant lectins: a review with emphasis on ArtinM properties. GLYCOCONJUGATE JOURNAL, v. 30, n. 7, p. 641-657, OCT 2013. Web of Science Citations: 55.
KIM, YEON J.; CARVALHO, FERNANDA C.; SOUZA, JOAO A. C.; GONCALVES, PEDRO C. G.; NOGUEIRA, ANDRESSA V. B.; SPOLIDORIO, LUIS C.; ROQUE-BARREIRA, MARIA C.; CIRELLI, JONI A. Topical application of the lectin Artin M accelerates wound healing in rat oral mucosa by enhancing TGF-beta and VEGF production. WOUND REPAIR AND REGENERATION, v. 21, n. 3, p. 456-463, MAY-JUN 2013. Web of Science Citations: 13.
PRANCHEVICIUS, MARIA-CRISTINA S.; OLIVEIRA, LEANDRO L.; ROSA, JOSE C.; AVANCI, NILTON C.; QUIAPIM, ANDREA C.; ROQUE-BARREIRA, MARIA-CRISTINA; GOLDMAN, MARIA-HELENA S. Characterization and optimization of ArtinM lectin expression in Escherichia coli. BMC Biotechnology, v. 12, AUG 2 2012. Web of Science Citations: 11.
RUAS, LUCIANA P.; CARVALHO, FERNANDA C.; ROQUE-BARREIRA, MARIA-CRISTINA. ArtinM offers new perspectives in the development of antifungal therapy. FRONTIERS IN MICROBIOLOGY, v. 3, 2012. Web of Science Citations: 7.
BORGES, CAROLINA BISINOTO; BERNARDES, EMERSON SOARES; LATORRACA, ELDER FRANCISCO; BECKER, ALINE PAIXAO; NEDER, LUCIANO; CHAMMAS, ROGER; ROQUE-BARREIRA, MARIA CRISTINA; MACHADO, HELIO RUBENS; DE OLIVEIRA, RICARDO SANTOS. Galectin-3 expression: a useful tool in the differential diagnosis of posterior fossa tumors in children. CHILD'S NERVOUS SYSTEM, v. 27, n. 2, p. 253-257, FEB 2011. Web of Science Citations: 5.
CARVALHO, FERNANDA CAROLINE; SOARES, SANDRO GOMES; TAMAROZZI, MIRELA BARROS; REGO, EDUARDO MAGALHAES; ROQUE-BARREIRA, MARIA-CRISTINA. The Recognition of N-Glycans by the Lectin ArtinM Mediates Cell Death of a Human Myeloid Leukemia Cell Line. PLoS One, v. 6, n. 11, p. e27892, 2011. Web of Science Citations: 17.
COLTRI, KELY C.; OLIVEIRA, LEANDRO L.; RUAS, LUCIANA P.; VENDRUSCOLO, PATRICIA E.; GOLDMAN, MARIA HELENA; PANUNTO-CASTELO, ADEMILSON; ROQUE-BARREIRA, MARIA-CRISTINA. Protection against Paracoccidioides brasiliensis infection conferred by the prophylactic administration of native and recombinant ArtinM. Medical Mycology, v. 48, n. 6, p. 792-799, SEP 2010. Web of Science Citations: 18.
DOS REIS ALMEIDA, FAUSTO BRUNO; DE OLIVEIRA, LEANDRO LICURSI; DE SOUSA, MARCELO VALLE; ROQUE BARREIRA, MARIA CRISTINA; HANNA, EBERT SEIXAS. Paracoccin from Paracoccidioides brasiliensis; purification through affinity with chitin and identification of N-acetyl-beta-D-glucosaminidase activity. YEAST, v. 27, n. 2, p. 67-76, FEB 2010. Web of Science Citations: 16.
DE ALMEIDA BURANELLO, PATRICIA ANDRESSA; ISNARD MOULIN, MARIA RAQUEL; SOUZA, JR., DEVANDIR ANTONIO; JAMUR, MARIA CELIA; ROQUE-BARREIRA, MARIA CRISTINA; OLIVER, CONSTANCE. The Lectin ArtinM Induces Recruitment of Rat Mast Cells from the Bone Marrow to the Peritoneal Cavity. PLoS One, v. 5, n. 3, p. e9776, 2010. Web of Science Citations: 9.
TOLEDO, KARINA ALVES; PEREIRA, FERNANDO LOURENCO; MAMBOLE, AGNES; LESAVRE, PHILIPPE; ROQUE-BARREIRA, MARIA CRISTINA; HALBWACHS-MECARELLI, LISE. The macrophage-derived neutrophil chemotactic factor, MNCF: A lectin with TNF-alpha-like activities on neutrophils. Biochemical and Biophysical Research Communications, v. 376, n. 4, p. 764-769, NOV 28 2008. Web of Science Citations: 1.

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