Immunodominant role of CCHA subunit of Concholepas hemocyanin is associated with unique biochemical properties

María Inés Becker, Alejandra Fuentes, Miguel Del Campo, Augusto Manubens, Esteban Nova, Harold Oliva, Fernando Faunes, María Antonieta Valenzuela, Marcelo Campos-Vallette, Alvaro Aliaga, Jorge Ferreira, Alfredo E. De Ioannes, Pablo De Ioannes, Bruno Moltedo

Resultado de la investigación: Article

26 Citas (Scopus)

Resumen

Hemocyanin, the oxygen transporter metallo-glycoprotein from mollusks, shows strong relationship between its notable structural features and intrinsic immunomodulatory effects. Here we investigated the individual contribution of CCHA and CCHB subunits from Concholepas hemocyanin (CCH) to in vivo humoral immune response and their pre-clinical evaluation as immunotherapeutic agent in a mice bladder cancer model, in relation to their biochemical properties. To this end, subunits were purified and well characterized. Homogeneous subunits were obtained by anionic exchange chromatography, and its purity assessed by electrophoretic and immunochemical methods. While each CCH subunit contains eight functional units showing partial cross reaction, the vibrational spectral analysis showed several spectral differences, suggesting structural differences between them. In addition, we demonstrated differences in the carbohydrate content: CCHA had a 3.6% w/w sugar with both N- and O-linked moieties. In turn, CCHB had a 2.5% w/w sugar with N-linked, while O-linked moieties were nearly absent. Considering these differences, it was not possible to predict a priori whether the immunogenic and immunotherapeutic properties of subunits might be similar. Surprisingly, both subunits by itself induced a humoral response, and showed an antitumor effect in the bladder carcinoma cell line MBT-2. However, when immunologic parameters were analyzed, CCHA showed better efficiency than CCHB. No allergic reactions or any toxic effects were observed in mice treated with CCHA, sustaining its potential therapeutic use. Our study supports that CCHA subunit accounts for the most important features involved in the immunogenicity of CCH, such as better hydrophilicity and higher content of carbohydrates.

Idioma originalEnglish
Páginas (desde-hasta)330-339
Número de páginas10
PublicaciónInternational Immunopharmacology
Volumen9
N.º3
DOI
EstadoPublished - 1 mar 2009

Huella dactilar

Hemocyanin
Carbohydrates
Mollusca
Poisons
Cross Reactions
Therapeutic Uses
Humoral Immunity
Hydrophobic and Hydrophilic Interactions
Urinary Bladder Neoplasms
Chromatography
Glycoproteins
Hypersensitivity
Urinary Bladder
Oxygen
Carcinoma
Cell Line

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

Citar esto

Becker, María Inés ; Fuentes, Alejandra ; Del Campo, Miguel ; Manubens, Augusto ; Nova, Esteban ; Oliva, Harold ; Faunes, Fernando ; Valenzuela, María Antonieta ; Campos-Vallette, Marcelo ; Aliaga, Alvaro ; Ferreira, Jorge ; De Ioannes, Alfredo E. ; De Ioannes, Pablo ; Moltedo, Bruno. / Immunodominant role of CCHA subunit of Concholepas hemocyanin is associated with unique biochemical properties. En: International Immunopharmacology. 2009 ; Vol. 9, N.º 3. pp. 330-339.
@article{c6bb86e97f9b4bd0984b60be0d198500,
title = "Immunodominant role of CCHA subunit of Concholepas hemocyanin is associated with unique biochemical properties",
abstract = "Hemocyanin, the oxygen transporter metallo-glycoprotein from mollusks, shows strong relationship between its notable structural features and intrinsic immunomodulatory effects. Here we investigated the individual contribution of CCHA and CCHB subunits from Concholepas hemocyanin (CCH) to in vivo humoral immune response and their pre-clinical evaluation as immunotherapeutic agent in a mice bladder cancer model, in relation to their biochemical properties. To this end, subunits were purified and well characterized. Homogeneous subunits were obtained by anionic exchange chromatography, and its purity assessed by electrophoretic and immunochemical methods. While each CCH subunit contains eight functional units showing partial cross reaction, the vibrational spectral analysis showed several spectral differences, suggesting structural differences between them. In addition, we demonstrated differences in the carbohydrate content: CCHA had a 3.6{\%} w/w sugar with both N- and O-linked moieties. In turn, CCHB had a 2.5{\%} w/w sugar with N-linked, while O-linked moieties were nearly absent. Considering these differences, it was not possible to predict a priori whether the immunogenic and immunotherapeutic properties of subunits might be similar. Surprisingly, both subunits by itself induced a humoral response, and showed an antitumor effect in the bladder carcinoma cell line MBT-2. However, when immunologic parameters were analyzed, CCHA showed better efficiency than CCHB. No allergic reactions or any toxic effects were observed in mice treated with CCHA, sustaining its potential therapeutic use. Our study supports that CCHA subunit accounts for the most important features involved in the immunogenicity of CCH, such as better hydrophilicity and higher content of carbohydrates.",
keywords = "Bladder cancer, CCHA and CCHB subunits characterization, Concholepas concholepas, Hemocyanin, Immunogen, Immunotherapy",
author = "Becker, {Mar{\'i}a In{\'e}s} and Alejandra Fuentes and {Del Campo}, Miguel and Augusto Manubens and Esteban Nova and Harold Oliva and Fernando Faunes and Valenzuela, {Mar{\'i}a Antonieta} and Marcelo Campos-Vallette and Alvaro Aliaga and Jorge Ferreira and {De Ioannes}, {Alfredo E.} and {De Ioannes}, Pablo and Bruno Moltedo",
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Becker, MI, Fuentes, A, Del Campo, M, Manubens, A, Nova, E, Oliva, H, Faunes, F, Valenzuela, MA, Campos-Vallette, M, Aliaga, A, Ferreira, J, De Ioannes, AE, De Ioannes, P & Moltedo, B 2009, 'Immunodominant role of CCHA subunit of Concholepas hemocyanin is associated with unique biochemical properties', International Immunopharmacology, vol. 9, n.º 3, pp. 330-339. https://doi.org/10.1016/j.intimp.2008.12.011

Immunodominant role of CCHA subunit of Concholepas hemocyanin is associated with unique biochemical properties. / Becker, María Inés; Fuentes, Alejandra; Del Campo, Miguel; Manubens, Augusto; Nova, Esteban; Oliva, Harold; Faunes, Fernando; Valenzuela, María Antonieta; Campos-Vallette, Marcelo; Aliaga, Alvaro; Ferreira, Jorge; De Ioannes, Alfredo E.; De Ioannes, Pablo; Moltedo, Bruno.

En: International Immunopharmacology, Vol. 9, N.º 3, 01.03.2009, p. 330-339.

Resultado de la investigación: Article

TY - JOUR

T1 - Immunodominant role of CCHA subunit of Concholepas hemocyanin is associated with unique biochemical properties

AU - Becker, María Inés

AU - Fuentes, Alejandra

AU - Del Campo, Miguel

AU - Manubens, Augusto

AU - Nova, Esteban

AU - Oliva, Harold

AU - Faunes, Fernando

AU - Valenzuela, María Antonieta

AU - Campos-Vallette, Marcelo

AU - Aliaga, Alvaro

AU - Ferreira, Jorge

AU - De Ioannes, Alfredo E.

AU - De Ioannes, Pablo

AU - Moltedo, Bruno

PY - 2009/3/1

Y1 - 2009/3/1

N2 - Hemocyanin, the oxygen transporter metallo-glycoprotein from mollusks, shows strong relationship between its notable structural features and intrinsic immunomodulatory effects. Here we investigated the individual contribution of CCHA and CCHB subunits from Concholepas hemocyanin (CCH) to in vivo humoral immune response and their pre-clinical evaluation as immunotherapeutic agent in a mice bladder cancer model, in relation to their biochemical properties. To this end, subunits were purified and well characterized. Homogeneous subunits were obtained by anionic exchange chromatography, and its purity assessed by electrophoretic and immunochemical methods. While each CCH subunit contains eight functional units showing partial cross reaction, the vibrational spectral analysis showed several spectral differences, suggesting structural differences between them. In addition, we demonstrated differences in the carbohydrate content: CCHA had a 3.6% w/w sugar with both N- and O-linked moieties. In turn, CCHB had a 2.5% w/w sugar with N-linked, while O-linked moieties were nearly absent. Considering these differences, it was not possible to predict a priori whether the immunogenic and immunotherapeutic properties of subunits might be similar. Surprisingly, both subunits by itself induced a humoral response, and showed an antitumor effect in the bladder carcinoma cell line MBT-2. However, when immunologic parameters were analyzed, CCHA showed better efficiency than CCHB. No allergic reactions or any toxic effects were observed in mice treated with CCHA, sustaining its potential therapeutic use. Our study supports that CCHA subunit accounts for the most important features involved in the immunogenicity of CCH, such as better hydrophilicity and higher content of carbohydrates.

AB - Hemocyanin, the oxygen transporter metallo-glycoprotein from mollusks, shows strong relationship between its notable structural features and intrinsic immunomodulatory effects. Here we investigated the individual contribution of CCHA and CCHB subunits from Concholepas hemocyanin (CCH) to in vivo humoral immune response and their pre-clinical evaluation as immunotherapeutic agent in a mice bladder cancer model, in relation to their biochemical properties. To this end, subunits were purified and well characterized. Homogeneous subunits were obtained by anionic exchange chromatography, and its purity assessed by electrophoretic and immunochemical methods. While each CCH subunit contains eight functional units showing partial cross reaction, the vibrational spectral analysis showed several spectral differences, suggesting structural differences between them. In addition, we demonstrated differences in the carbohydrate content: CCHA had a 3.6% w/w sugar with both N- and O-linked moieties. In turn, CCHB had a 2.5% w/w sugar with N-linked, while O-linked moieties were nearly absent. Considering these differences, it was not possible to predict a priori whether the immunogenic and immunotherapeutic properties of subunits might be similar. Surprisingly, both subunits by itself induced a humoral response, and showed an antitumor effect in the bladder carcinoma cell line MBT-2. However, when immunologic parameters were analyzed, CCHA showed better efficiency than CCHB. No allergic reactions or any toxic effects were observed in mice treated with CCHA, sustaining its potential therapeutic use. Our study supports that CCHA subunit accounts for the most important features involved in the immunogenicity of CCH, such as better hydrophilicity and higher content of carbohydrates.

KW - Bladder cancer

KW - CCHA and CCHB subunits characterization

KW - Concholepas concholepas

KW - Hemocyanin

KW - Immunogen

KW - Immunotherapy

UR - http://www.scopus.com/inward/record.url?scp=60249102375&partnerID=8YFLogxK

U2 - 10.1016/j.intimp.2008.12.011

DO - 10.1016/j.intimp.2008.12.011

M3 - Article

C2 - 19159699

AN - SCOPUS:60249102375

VL - 9

SP - 330

EP - 339

JO - International Immunopharmacology

JF - International Immunopharmacology

SN - 1567-5769

IS - 3

ER -