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Bioética en Latinoamérica : articulaciones entre bioética, biopolítica y colonialidad
(Universidad de Chile, 2017)
Derecho a la autodeterminación informativa respecto a los datos genéticos
(Universidad de Chile, 2018)
Participación de receptores lectina tipo C en el reconocimiento de hemocianinas de moluscos por células presentadoras de antígeno y consecuencias en la presentación antigénica
(2016)
biomedicina como proteína carrier de antígenos tumorales y como inmunoestimulantes no específicos en el tratamiento de ciertos cáncer. Para explicar esta propiedad se han invocado características tales como su tamaño, xenogenicidad, estructura compleja y...
Hemocyanins from the gastropod Megathura crenulata (KLH), Concholepas concholepas (CCH) and Fissurella latimarginata (FLH) have mainly been used as non-specific immunostimulants with beneficial clinical outcomes, to prevent the progression of recurrent superficial bladder cancer or as carriers/adjuvants for producing antibodies against tumor-associated antigens in therapeutic vaccines against cancer. However, the mechanism involved in the positive immunomodulatory effects of these proteins has been scarcely studied. An important feature of these hemocyanins is its carbohydrate content, which can reach up to 3% (w/w), being mannose as the most abundant sugar. These oligosaccharides can be recognized by C-type lectin receptors (CLRs) of innate immunity, such as Mannose Receptor (MR), DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin) or MGL (macrophage galactose lectine), present on antigen presenting cells (APCs). Furthermore, these innate receptors have been involved in classical and alternative antigen presentation by MHC I and MHC II to CD8+ and CD4+ lymphocytes, respectively. Hence, we proposed that CLRs-mediated endocytosis of hemocyanins in antigen presenting cells triggers the cross-presentation of these proteins. In this work, we studied the interaction between CLRs and hemocyanins using indirect ELISA and SPR (surface plasmon resonance). We found that CCH, FLH, and KLH bind to MR and DC-SIGN with high affinity constants; additionally FLH and KLH also bind to MGL. Our results demonstrate that the interaction between MR and hemocyanins trigger their endocytosis, analysed by an artificial CHO-MR system. Furthermore, human and murine APCs-expressing CLRs can uptake hemocyanins and ovalbumin. We also found that hemocyanins uptake by murine macrophages and dendritic cells can be partially inhibited by EDTA and D-Mannose. These results suggest an important role of CLRs in endocytosis and signalling transduction of hemocyanins. On the other hand, we studied the cellular destination of hemocyanins in bone marrow derived dendritic cells (BMDCs) using confocal microscopy. FLH and KLH showed a similar localization in Rab5+, Rab7+ and Lamp-1+ compartments. However, CCH was not found in Rab5+ early endosomes, suggesting differential compartmentalization between the hemocyanins. Thus, FLH and KLH could be involved in an alternative processing pathway such as cross-presentation. Finally, we determined if murine APCs could present hemocyanins on MHC I context. Our results showed that in vitro stimulation of macrophages with FLH, but not with CCH or KLH, increased MHC I and MHC II expression, supporting our hypothesis. Hemocyanins cross-presentation could explain one of the mechanisms involved in the antitumoral effect of these proteins, in addition to the classic presentation by MHC II. Moreover, CD8+ lymphocytes activation could promote cytokines and humoral factors release that indirectly trigger other latent immune responses against the tumoral cells, effect known as bystander effect...
Hemocyanins from the gastropod Megathura crenulata (KLH), Concholepas concholepas (CCH) and Fissurella latimarginata (FLH) have mainly been used as non-specific immunostimulants with beneficial clinical outcomes, to prevent the progression of recurrent superficial bladder cancer or as carriers/adjuvants for producing antibodies against tumor-associated antigens in therapeutic vaccines against cancer. However, the mechanism involved in the positive immunomodulatory effects of these proteins has been scarcely studied. An important feature of these hemocyanins is its carbohydrate content, which can reach up to 3% (w/w), being mannose as the most abundant sugar. These oligosaccharides can be recognized by C-type lectin receptors (CLRs) of innate immunity, such as Mannose Receptor (MR), DC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin) or MGL (macrophage galactose lectine), present on antigen presenting cells (APCs). Furthermore, these innate receptors have been involved in classical and alternative antigen presentation by MHC I and MHC II to CD8+ and CD4+ lymphocytes, respectively. Hence, we proposed that CLRs-mediated endocytosis of hemocyanins in antigen presenting cells triggers the cross-presentation of these proteins. In this work, we studied the interaction between CLRs and hemocyanins using indirect ELISA and SPR (surface plasmon resonance). We found that CCH, FLH, and KLH bind to MR and DC-SIGN with high affinity constants; additionally FLH and KLH also bind to MGL. Our results demonstrate that the interaction between MR and hemocyanins trigger their endocytosis, analysed by an artificial CHO-MR system. Furthermore, human and murine APCs-expressing CLRs can uptake hemocyanins and ovalbumin. We also found that hemocyanins uptake by murine macrophages and dendritic cells can be partially inhibited by EDTA and D-Mannose. These results suggest an important role of CLRs in endocytosis and signalling transduction of hemocyanins. On the other hand, we studied the cellular destination of hemocyanins in bone marrow derived dendritic cells (BMDCs) using confocal microscopy. FLH and KLH showed a similar localization in Rab5+, Rab7+ and Lamp-1+ compartments. However, CCH was not found in Rab5+ early endosomes, suggesting differential compartmentalization between the hemocyanins. Thus, FLH and KLH could be involved in an alternative processing pathway such as cross-presentation. Finally, we determined if murine APCs could present hemocyanins on MHC I context. Our results showed that in vitro stimulation of macrophages with FLH, but not with CCH or KLH, increased MHC I and MHC II expression, supporting our hypothesis. Hemocyanins cross-presentation could explain one of the mechanisms involved in the antitumoral effect of these proteins, in addition to the classic presentation by MHC II. Moreover, CD8+ lymphocytes activation could promote cytokines and humoral factors release that indirectly trigger other latent immune responses against the tumoral cells, effect known as bystander effect...
Efecto inmunomodulador de hemocianinas de moluscos combinadas con adyuvantes de vacuna en cáncer oral murino
(Universidad de Chile, 2015)
: polysorbate 20 / polisorbato 20
1
RESUMEN
Las hemocianinas de algunos moluscos son ampliamente usadas en
biomedicina, entre ellas, la de Megathura crenulata (KLH), de Concholepas
concholepas (CCH) y de Fissurella latimarginata (FLH), éstas dos...
. Luego de más de 35 años de uso en biomedicina, los investigadores han provisto evidencia que sustenta este atributo, al tener la habilidad para incrementar la respuesta inmune del hospedero, a través de su interacción con diferentes células inmunes...
. Luego de más de 35 años de uso en biomedicina, los investigadores han provisto evidencia que sustenta este atributo, al tener la habilidad para incrementar la respuesta inmune del hospedero, a través de su interacción con diferentes células inmunes...
Síntesis y caracterización de nanopartículas de níquel, cobalto y mezclas níquel-cobalto dispersadas en diferentes matrices
(Universidad de Chile, 2015)
literatura para catálisis homogénea con
metales de transición.
11
ÍNDICE DE TABLAS
1. Aplicaciones de las propiedades magnéticas en biomedicina
2. Materiales magnéticos y sus aplicaciones
3. Resumen de parámetros magnéticos...
aplicaciones presentes y futuras, las más interesantes quizás en el campo de la biomedicina [3]. El origen en el cambio de estas propiedades comparadas con el material macroscópico o “bulk”, se debe a que la reducción de tamaño, 19 produce cambios en los...
aplicaciones presentes y futuras, las más interesantes quizás en el campo de la biomedicina [3]. El origen en el cambio de estas propiedades comparadas con el material macroscópico o “bulk”, se debe a que la reducción de tamaño, 19 produce cambios en los...
Manifiesto Florence para unos mejores cuidados basados en la evidencia
(Ediciones Rol, 2020)
in Evidence-Based Health Care.
University of Oxford. Oxford. UK.
josepmariagarciaa@gmail.com
RAMÓN ESCURIET PEIRÓ
PhD Biomedicina. Director del Programa
de formación teórica de matronas. Departament
de Salut. Generalitat de Catalunya. Barcelona.
NÚRIA...
Estudio del rol de la caspasa 8 en la infección por Trypanosoma cruzi en una linea celular de trofoblasto humano (Be Wo)
(Universidad de Chile, 2016)
Vanessa V. Carrillo Werner
TESIS PARA OPTAR AL GRADO DE MAGISTER EN BIOMEDICINA CELULAR Y
MOLECULAR
Director de Tesis: Dra. Ulrike Kemmerling
2016
AGRADECIMIENTOS
Quisiera dar mi más profundo agradecimiento a mi tutora, la Dra...
Problemas bioéticos de la investigación biomédica con pueblos indígenas de Chile
(2010)
en la biomedicina es una cuestión
particularmente relevante, y es posible visualizar la
existencia de intereses y conflictos de interés nacionales
y trasnacionales que operan de manera encubierta o
explícita en distintos niveles o “arenas”, desde...
La neuroinflamación como factor detonante del desarrollo de la enfermedad de Alzheimer
(Sociedad de Neurología, Psiquiatría y Neurocirugía, 2010-03-03)
/03/2010
Laboratorio de Neurociencias Celulares y Moleculares, Facultad de Ciencias, Universidad de Chile y Centro Internacional de
Biomedicina (ICC):
1 Tesista Ingeniería en Biotecnología Molecular, Universidad de Chile.
2 M.D.
3 Ph.D.
ARTÍCULO DE REVISIÓN...
Encapsulación de biomoléculas usando polímeros naturales: “Un nuevo enfoque en la entrega defFármacos en medicina”
(Universidad de Chile, 2013)
fascinante a desarrollar en el campo de la
biomedicina.
3.2. Biomateriales inorgánicos
Para el desarrollo de estos biomateriales
en la entrega de fármacos y/o agentes bioactivos
diversos autores han utilizado alginato y quitosano
de manera individual...