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Hypoxia-induced complement dysregulation is associated with microvascular impairments in mouse tracheal transplants

BACKGROUND: Complement Regulatory Proteins (CRPs), especially CD55 primarily negate complement factor 3-mediated injuries and maintain tissue homeostasis during complement cascade activation. Complement activation and regulation during alloimmune inflammation contribute to allograft injury and there...

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Autores principales: Khan, Mohammad Afzal, Shamma, Talal, Kazmi, Shadab, Altuhami, Abdullah, Ahmed, Hala Abdalrahman, Assiri, Abdullah Mohammed, Broering, Dieter Clemens
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110829/
https://www.ncbi.nlm.nih.gov/pubmed/32234039
http://dx.doi.org/10.1186/s12967-020-02305-z
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author Khan, Mohammad Afzal
Shamma, Talal
Kazmi, Shadab
Altuhami, Abdullah
Ahmed, Hala Abdalrahman
Assiri, Abdullah Mohammed
Broering, Dieter Clemens
author_facet Khan, Mohammad Afzal
Shamma, Talal
Kazmi, Shadab
Altuhami, Abdullah
Ahmed, Hala Abdalrahman
Assiri, Abdullah Mohammed
Broering, Dieter Clemens
author_sort Khan, Mohammad Afzal
collection PubMed
description BACKGROUND: Complement Regulatory Proteins (CRPs), especially CD55 primarily negate complement factor 3-mediated injuries and maintain tissue homeostasis during complement cascade activation. Complement activation and regulation during alloimmune inflammation contribute to allograft injury and therefore we proposed to investigate a crucial pathological link between vascular expression of CD55, active-C3, T cell immunity and associated microvascular tissue injuries during allograft rejection. METHODS: Balb/c→C57BL/6 allografts were examined for microvascular deposition of CD55, C3d, T cells, and associated tissue microvascular impairments during rejection in mouse orthotopic tracheal transplantation. RESULTS: Our findings demonstrated that hypoxia-induced early activation of HIF-1α favors a cell-mediated inflammation (CD4(+), CD8(+), and associated proinflammatory cytokines, IL-2 and TNF-α), which proportionally triggers the downregulation of CRP-CD55, and thereby augments the uncontrolled release of active-C3, and Caspase-3 deposition on CD31(+) graft vascular endothelial cells. These molecular changes are pathologically associated with microvascular deterioration (low tissue O(2) and Blood flow) and subsequent airway epithelial injuries of rejecting allografts as compared to non-rejecting syngrafts. CONCLUSION: Together, these findings establish a pathological correlation between complement dysregulation, T cell immunity, and microvascular associated injuries during alloimmune inflammation in transplantation.
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spelling pubmed-71108292020-04-07 Hypoxia-induced complement dysregulation is associated with microvascular impairments in mouse tracheal transplants Khan, Mohammad Afzal Shamma, Talal Kazmi, Shadab Altuhami, Abdullah Ahmed, Hala Abdalrahman Assiri, Abdullah Mohammed Broering, Dieter Clemens J Transl Med Research BACKGROUND: Complement Regulatory Proteins (CRPs), especially CD55 primarily negate complement factor 3-mediated injuries and maintain tissue homeostasis during complement cascade activation. Complement activation and regulation during alloimmune inflammation contribute to allograft injury and therefore we proposed to investigate a crucial pathological link between vascular expression of CD55, active-C3, T cell immunity and associated microvascular tissue injuries during allograft rejection. METHODS: Balb/c→C57BL/6 allografts were examined for microvascular deposition of CD55, C3d, T cells, and associated tissue microvascular impairments during rejection in mouse orthotopic tracheal transplantation. RESULTS: Our findings demonstrated that hypoxia-induced early activation of HIF-1α favors a cell-mediated inflammation (CD4(+), CD8(+), and associated proinflammatory cytokines, IL-2 and TNF-α), which proportionally triggers the downregulation of CRP-CD55, and thereby augments the uncontrolled release of active-C3, and Caspase-3 deposition on CD31(+) graft vascular endothelial cells. These molecular changes are pathologically associated with microvascular deterioration (low tissue O(2) and Blood flow) and subsequent airway epithelial injuries of rejecting allografts as compared to non-rejecting syngrafts. CONCLUSION: Together, these findings establish a pathological correlation between complement dysregulation, T cell immunity, and microvascular associated injuries during alloimmune inflammation in transplantation. BioMed Central 2020-03-31 /pmc/articles/PMC7110829/ /pubmed/32234039 http://dx.doi.org/10.1186/s12967-020-02305-z Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Khan, Mohammad Afzal
Shamma, Talal
Kazmi, Shadab
Altuhami, Abdullah
Ahmed, Hala Abdalrahman
Assiri, Abdullah Mohammed
Broering, Dieter Clemens
Hypoxia-induced complement dysregulation is associated with microvascular impairments in mouse tracheal transplants
title Hypoxia-induced complement dysregulation is associated with microvascular impairments in mouse tracheal transplants
title_full Hypoxia-induced complement dysregulation is associated with microvascular impairments in mouse tracheal transplants
title_fullStr Hypoxia-induced complement dysregulation is associated with microvascular impairments in mouse tracheal transplants
title_full_unstemmed Hypoxia-induced complement dysregulation is associated with microvascular impairments in mouse tracheal transplants
title_short Hypoxia-induced complement dysregulation is associated with microvascular impairments in mouse tracheal transplants
title_sort hypoxia-induced complement dysregulation is associated with microvascular impairments in mouse tracheal transplants
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7110829/
https://www.ncbi.nlm.nih.gov/pubmed/32234039
http://dx.doi.org/10.1186/s12967-020-02305-z
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