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Low pH impairs complement-dependent cytotoxicity against IgG-coated target cells

Local acidosis is a common feature of allergic, vascular, autoimmune, and cancer diseases. However, few studies have addressed the effect of extracellular pH on the immune response. Here, we analyzed whether low pH could modulate complement-dependent cytotoxicity (CDC) against IgG-coated cells. Usin...

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Autores principales: Dantas, Ezequiel, Díaz, Fernando Erra, Gerber, Pehuén Pereyra, Merlotti, Antonela, Varese, Augusto, Ostrowski, Matías, Sabatté, Juan, Geffner, Jorge
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342046/
https://www.ncbi.nlm.nih.gov/pubmed/27716623
http://dx.doi.org/10.18632/oncotarget.12412
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author Dantas, Ezequiel
Díaz, Fernando Erra
Gerber, Pehuén Pereyra
Merlotti, Antonela
Varese, Augusto
Ostrowski, Matías
Sabatté, Juan
Geffner, Jorge
author_facet Dantas, Ezequiel
Díaz, Fernando Erra
Gerber, Pehuén Pereyra
Merlotti, Antonela
Varese, Augusto
Ostrowski, Matías
Sabatté, Juan
Geffner, Jorge
author_sort Dantas, Ezequiel
collection PubMed
description Local acidosis is a common feature of allergic, vascular, autoimmune, and cancer diseases. However, few studies have addressed the effect of extracellular pH on the immune response. Here, we analyzed whether low pH could modulate complement-dependent cytotoxicity (CDC) against IgG-coated cells. Using human serum as a complement source, we found that extracellular pH values of 5.5 and 6.0 strongly inhibit CDC against either B lymphoblast cell lines coated with the chimeric anti-CD20 mAb rituximab or PBMCs coated with the humanized anti-CD52 mAb alemtuzumab. Suppression of CDC by low pH was observed either in cells suspended in culture medium or in whole blood assays. Interestingly, not only CDC against IgG-coated cells, but also the activation of the complement system induced by the alternative and lectin pathways was prevented by low pH. Tumor-targeting mAbs represent one of the most successful tools for cancer therapy, however, the use of mAb monotherapy has only modest effects on solid tumors. Our present results suggest that severe acidosis, a hallmark of solid tumors, might impair complement-mediated tumor destruction directed by mAb.
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spelling pubmed-53420462017-03-27 Low pH impairs complement-dependent cytotoxicity against IgG-coated target cells Dantas, Ezequiel Díaz, Fernando Erra Gerber, Pehuén Pereyra Merlotti, Antonela Varese, Augusto Ostrowski, Matías Sabatté, Juan Geffner, Jorge Oncotarget Research Paper Local acidosis is a common feature of allergic, vascular, autoimmune, and cancer diseases. However, few studies have addressed the effect of extracellular pH on the immune response. Here, we analyzed whether low pH could modulate complement-dependent cytotoxicity (CDC) against IgG-coated cells. Using human serum as a complement source, we found that extracellular pH values of 5.5 and 6.0 strongly inhibit CDC against either B lymphoblast cell lines coated with the chimeric anti-CD20 mAb rituximab or PBMCs coated with the humanized anti-CD52 mAb alemtuzumab. Suppression of CDC by low pH was observed either in cells suspended in culture medium or in whole blood assays. Interestingly, not only CDC against IgG-coated cells, but also the activation of the complement system induced by the alternative and lectin pathways was prevented by low pH. Tumor-targeting mAbs represent one of the most successful tools for cancer therapy, however, the use of mAb monotherapy has only modest effects on solid tumors. Our present results suggest that severe acidosis, a hallmark of solid tumors, might impair complement-mediated tumor destruction directed by mAb. Impact Journals LLC 2016-10-03 /pmc/articles/PMC5342046/ /pubmed/27716623 http://dx.doi.org/10.18632/oncotarget.12412 Text en Copyright: © 2016 Dantas et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Dantas, Ezequiel
Díaz, Fernando Erra
Gerber, Pehuén Pereyra
Merlotti, Antonela
Varese, Augusto
Ostrowski, Matías
Sabatté, Juan
Geffner, Jorge
Low pH impairs complement-dependent cytotoxicity against IgG-coated target cells
title Low pH impairs complement-dependent cytotoxicity against IgG-coated target cells
title_full Low pH impairs complement-dependent cytotoxicity against IgG-coated target cells
title_fullStr Low pH impairs complement-dependent cytotoxicity against IgG-coated target cells
title_full_unstemmed Low pH impairs complement-dependent cytotoxicity against IgG-coated target cells
title_short Low pH impairs complement-dependent cytotoxicity against IgG-coated target cells
title_sort low ph impairs complement-dependent cytotoxicity against igg-coated target cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342046/
https://www.ncbi.nlm.nih.gov/pubmed/27716623
http://dx.doi.org/10.18632/oncotarget.12412
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