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The Proteomic Profile of Circulating Pentraxin 3 (PTX3) Complex in Sepsis Demonstrates the Interaction with Azurocidin 1 and Other Components of Neutrophil Extracellular Traps

Pentraxin 3 (PTX3), a long pentraxin subfamily member in the pentraxin family, plays an important role in innate immunity as a soluble pattern recognition receptor. Plasma PTX3 is elevated in sepsis (∼200 ng/ml) and correlates with mortality. The roles of PTX3 in sepsis, however, are not well unders...

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Autores principales: Daigo, Kenji, Yamaguchi, Naotaka, Kawamura, Takeshi, Matsubara, Koichi, Jiang, Shuying, Ohashi, Riuko, Sudou, Yukio, Kodama, Tatsuhiko, Naito, Makoto, Inoue, Kenji, Hamakubo, Takao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Biochemistry and Molecular Biology 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3433926/
https://www.ncbi.nlm.nih.gov/pubmed/22278372
http://dx.doi.org/10.1074/mcp.M111.015073
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author Daigo, Kenji
Yamaguchi, Naotaka
Kawamura, Takeshi
Matsubara, Koichi
Jiang, Shuying
Ohashi, Riuko
Sudou, Yukio
Kodama, Tatsuhiko
Naito, Makoto
Inoue, Kenji
Hamakubo, Takao
author_facet Daigo, Kenji
Yamaguchi, Naotaka
Kawamura, Takeshi
Matsubara, Koichi
Jiang, Shuying
Ohashi, Riuko
Sudou, Yukio
Kodama, Tatsuhiko
Naito, Makoto
Inoue, Kenji
Hamakubo, Takao
author_sort Daigo, Kenji
collection PubMed
description Pentraxin 3 (PTX3), a long pentraxin subfamily member in the pentraxin family, plays an important role in innate immunity as a soluble pattern recognition receptor. Plasma PTX3 is elevated in sepsis (∼200 ng/ml) and correlates with mortality. The roles of PTX3 in sepsis, however, are not well understood. To investigate the ligands of PTX3 in sepsis, we performed a targeted proteomic study of circulating PTX3 complexes using magnetic bead-based immunopurification and shotgun proteomics for label-free relative quantitation via spectral counting. From septic patient fluids, we successfully identified 104 candidate proteins, including the known PTX3-interacting proteins involved in complement activation, pathogen opsonization, inflammation regulation, and extracellular matrix deposition. Notably, the proteomic profile additionally showed that PTX3 formed a complex with some of the components of neutrophil extracellular traps. Subsequent biochemical analyses revealed a direct interaction of bactericidal proteins azurocidin 1 (AZU1) and myeloperoxidase with PTX3. AZU1 exhibited high affinity binding (K(D) = 22 ± 7.6 nm) to full-length PTX3 in a calcium ion-dependent manner and bound specifically to an oligomer of the PTX3 N-terminal domain. Immunohistochemistry with a specific monoclonal antibody generated against AZU1 revealed a partial co-localization of AZU1 with PTX3 in neutrophil extracellular traps. The association of circulating PTX3 with components of the neutrophil extracellular traps in sepsis suggests a role for PTX3 in host defense and as a potential diagnostic target.
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spelling pubmed-34339262012-09-11 The Proteomic Profile of Circulating Pentraxin 3 (PTX3) Complex in Sepsis Demonstrates the Interaction with Azurocidin 1 and Other Components of Neutrophil Extracellular Traps Daigo, Kenji Yamaguchi, Naotaka Kawamura, Takeshi Matsubara, Koichi Jiang, Shuying Ohashi, Riuko Sudou, Yukio Kodama, Tatsuhiko Naito, Makoto Inoue, Kenji Hamakubo, Takao Mol Cell Proteomics Research Pentraxin 3 (PTX3), a long pentraxin subfamily member in the pentraxin family, plays an important role in innate immunity as a soluble pattern recognition receptor. Plasma PTX3 is elevated in sepsis (∼200 ng/ml) and correlates with mortality. The roles of PTX3 in sepsis, however, are not well understood. To investigate the ligands of PTX3 in sepsis, we performed a targeted proteomic study of circulating PTX3 complexes using magnetic bead-based immunopurification and shotgun proteomics for label-free relative quantitation via spectral counting. From septic patient fluids, we successfully identified 104 candidate proteins, including the known PTX3-interacting proteins involved in complement activation, pathogen opsonization, inflammation regulation, and extracellular matrix deposition. Notably, the proteomic profile additionally showed that PTX3 formed a complex with some of the components of neutrophil extracellular traps. Subsequent biochemical analyses revealed a direct interaction of bactericidal proteins azurocidin 1 (AZU1) and myeloperoxidase with PTX3. AZU1 exhibited high affinity binding (K(D) = 22 ± 7.6 nm) to full-length PTX3 in a calcium ion-dependent manner and bound specifically to an oligomer of the PTX3 N-terminal domain. Immunohistochemistry with a specific monoclonal antibody generated against AZU1 revealed a partial co-localization of AZU1 with PTX3 in neutrophil extracellular traps. The association of circulating PTX3 with components of the neutrophil extracellular traps in sepsis suggests a role for PTX3 in host defense and as a potential diagnostic target. The American Society for Biochemistry and Molecular Biology 2012-06 2012-01-25 /pmc/articles/PMC3433926/ /pubmed/22278372 http://dx.doi.org/10.1074/mcp.M111.015073 Text en © 2012 by The American Society for Biochemistry and Molecular Biology, Inc. Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) applies to Author Choice Articles
spellingShingle Research
Daigo, Kenji
Yamaguchi, Naotaka
Kawamura, Takeshi
Matsubara, Koichi
Jiang, Shuying
Ohashi, Riuko
Sudou, Yukio
Kodama, Tatsuhiko
Naito, Makoto
Inoue, Kenji
Hamakubo, Takao
The Proteomic Profile of Circulating Pentraxin 3 (PTX3) Complex in Sepsis Demonstrates the Interaction with Azurocidin 1 and Other Components of Neutrophil Extracellular Traps
title The Proteomic Profile of Circulating Pentraxin 3 (PTX3) Complex in Sepsis Demonstrates the Interaction with Azurocidin 1 and Other Components of Neutrophil Extracellular Traps
title_full The Proteomic Profile of Circulating Pentraxin 3 (PTX3) Complex in Sepsis Demonstrates the Interaction with Azurocidin 1 and Other Components of Neutrophil Extracellular Traps
title_fullStr The Proteomic Profile of Circulating Pentraxin 3 (PTX3) Complex in Sepsis Demonstrates the Interaction with Azurocidin 1 and Other Components of Neutrophil Extracellular Traps
title_full_unstemmed The Proteomic Profile of Circulating Pentraxin 3 (PTX3) Complex in Sepsis Demonstrates the Interaction with Azurocidin 1 and Other Components of Neutrophil Extracellular Traps
title_short The Proteomic Profile of Circulating Pentraxin 3 (PTX3) Complex in Sepsis Demonstrates the Interaction with Azurocidin 1 and Other Components of Neutrophil Extracellular Traps
title_sort proteomic profile of circulating pentraxin 3 (ptx3) complex in sepsis demonstrates the interaction with azurocidin 1 and other components of neutrophil extracellular traps
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3433926/
https://www.ncbi.nlm.nih.gov/pubmed/22278372
http://dx.doi.org/10.1074/mcp.M111.015073
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