RESUMO
BACKGROUND: Mast cells are hematopoietically derived cells that play a role in inflammatory processes such as allergy, as well as in the immune response against pathogens by the selective and rapid release of preformed and lipid mediators, and the delayed release of cytokines. The native homotetrameric lectin ArtinM, a D-mannose binding lectin purified from Artocarpus heterophyllus seeds, is one of several lectins that are able to activate mast cells. Besides activating mast cells, ArtinM has been shown to affect several biological responses, including immunomodulation and acceleration of wound healing. Because of the potential pharmacological application of ArtinM, a recombinant ArtinM (rArtinM) was produced in Escherichia coli. The current study evaluated the ability of rArtinM to induce mast cell degranulation and activation. RESULTS: The glycan binding specificity of rArtinM was similar to that of jArtinM. rArtinM, via its CRD, was able to degranulate, releasing ß-hexosaminidase and TNF-α, and to promote morphological changes on the mast cell surface. Moreover, rArtinM induced the release of the newly-synthesized mediator, IL-4. rArtinM does not have a co-stimulatory effect on the FcεRI degranulation via. The IgE-dependent mast cell activation triggered by rArtinM seems to be dependent on NFkB activation. CONCLUSIONS: The lectin rArtinM has the ability to activate and degranulate mast cells via their CRDs. The present study indicates that rArtinM is a suitable substitute for the native form, jArtinM, and that rArtinM may serve as an important and reliable pharmacological agent.
Assuntos
Mastócitos/imunologia , Lectinas de Plantas/imunologia , Proteínas Recombinantes/imunologia , Animais , Artocarpus/imunologia , Degranulação Celular , Linhagem Celular , Clonagem Molecular , Escherichia coli/genética , Histamina/metabolismo , Imunoglobulina E/metabolismo , Imunomodulação , Interleucina-4/metabolismo , Manose/metabolismo , NF-kappa B/metabolismo , Lectinas de Plantas/isolamento & purificação , Ligação Proteica , Ratos , Proteínas Recombinantes/isolamento & purificação , beta-N-Acetil-Hexosaminidases/metabolismoRESUMO
Advances in the glycobiology and immunology fields have provided many insights into the role of carbohydrate-protein interactions in the immune system. We aim to present a comprehensive review of the effects that some plant lectins exert as immunomodulatory agents, showing that they are able to positively modify the immune response to certain pathological conditions, such as cancer and infections. The present review comprises four main themes: (1) an overview of plant lectins that exert immunomodulatory effects and the mechanisms accounting for these activities; (2) general characteristics of the immunomodulatory lectin ArtinM from the seeds of Artocarpus heterophyllus; (3) activation of innate immunity cells by ArtinM and consequent induction of Th1 immunity; (4) resistance conferred by ArtinM administration in infections with intracellular pathogens, such as Leishmania (Leishmania) major, Leishmania (Leishmania) amazonensis, and Paracoccidioides brasiliensis. We believe that this review will be a valuable resource for more studies in this relatively neglected area of research, which has the potential to reveal carbohydrate targets for novel prophylactic and therapeutic strategies.
Assuntos
Fatores Imunológicos/farmacologia , Lectinas de Plantas/farmacologia , Animais , Artocarpus/química , Artocarpus/imunologia , Humanos , Imunidade Inata/efeitos dos fármacos , Fatores Imunológicos/química , Fatores Imunológicos/imunologia , Lectinas de Plantas/química , Lectinas de Plantas/imunologia , Células Th1/efeitos dos fármacos , Células Th1/imunologiaRESUMO
The immunoregulatory effect of Artin M and jacalin from extract of Artocarpus integrifolia seeds (jack extract) against infection with Candida albicans was investigated. Swiss mice received jack extract containing 500 µg protein/ml PBS intraperitoneally (i.p.) or PBS alone and after 72 h were infected i.p. with C. albicans CR15 (10(7)) and sacrificed after 30 min, 2, 6, 24, and 72 h. ELISA analysis revealed that in jack extract-treated mice IFN-γ was predominantly produced versus IL-10 in control mice. These results suggest that jack extract induced a protective immune response, since C. albicans clearance was complete at 72 h postinfection. Jack extract presents two lectins (Artin M and jacalin) with distinct biological properties. Artin M was able to induce IL-12 production by macrophages. Also, Artin M in different concentrations, associated with jacalin or in jack extract induced both IFN-γ and IL-17 production. As a consequence, phagocytic and candidacidal activity increased significantly. Alanine aminotransferase activity (ALT) was used as parameter for damage of the liver. The activity of ALT correlated with inoculum size that increased significantly in control group, however, mice pretreated with jack extract 3 days before infection presented normal ALT. Mice pretreated with jack extract that received a lethal inoculum of Candida presented 90% survival versus 20% among controls or mice pretreated with jacalin. Thus, the results suggest that Artin M by itself, associated with jacalin or present in jack extract is able to induce protective Th1 and Th17 immune responses against Candida albicans infection.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Candida albicans/imunologia , Candidíase/imunologia , Fitoterapia , Extratos Vegetais/administração & dosagem , Lectinas de Plantas/administração & dosagem , Células Th1/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Adjuvantes Imunológicos/efeitos adversos , Alanina Transaminase/genética , Alanina Transaminase/imunologia , Alanina Transaminase/metabolismo , Animais , Artocarpus/imunologia , Candida albicans/patogenicidade , Candidíase/prevenção & controle , Citocinas/genética , Citocinas/imunologia , Citocinas/metabolismo , Ativação Enzimática/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/imunologia , Imunidade/efeitos dos fármacos , Lectinas/administração & dosagem , Lectinas/efeitos adversos , Camundongos , Extratos Vegetais/efeitos adversos , Lectinas de Plantas/efeitos adversos , Sementes , Células Th1/imunologia , Células Th1/metabolismo , Células Th1/patologia , Células Th17/imunologia , Células Th17/metabolismo , Células Th17/patologiaRESUMO
Did you know that January 22nd, 1999 marked 206 years since the arrival of the breadfruit in the Caribbean? This issue of NYAM NEWS continues with the series of 'Knowing our foods', highlighting their history, the nutrients they provide and some interesting ways in which they can be used in our meals. Breadfruit is the focus of this issue.