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Integrin α4β1/VCAM-1 Interaction Evokes Dynamic Cell Aggregation Between Immune Cells and Human Lung Microvascular Endothelial Cells at Infectious Hemolysis

Bacterial and viral infection is a common cause of pneumonia, respiratory failure, and even acute respiratory distress syndrome. Increasing evidence indicates that red blood cells (RBCs) may contribute to immune response and inflammation. However, the precise molecular mechanisms that link RBC and h...

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Autores principales: Lou, Hai-Yan, Yan, Hai-Peng, Yang, Long-Gui, Fan, Jiang-hua, Cho, William C., Xiao, Zheng-hui, Li, Shuang-Jie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093802/
https://www.ncbi.nlm.nih.gov/pubmed/33959020
http://dx.doi.org/10.3389/fphar.2021.653143
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author Lou, Hai-Yan
Yan, Hai-Peng
Yang, Long-Gui
Fan, Jiang-hua
Cho, William C.
Xiao, Zheng-hui
Li, Shuang-Jie
author_facet Lou, Hai-Yan
Yan, Hai-Peng
Yang, Long-Gui
Fan, Jiang-hua
Cho, William C.
Xiao, Zheng-hui
Li, Shuang-Jie
author_sort Lou, Hai-Yan
collection PubMed
description Bacterial and viral infection is a common cause of pneumonia, respiratory failure, and even acute respiratory distress syndrome. Increasing evidence indicates that red blood cells (RBCs) may contribute to immune response and inflammation. However, the precise molecular mechanisms that link RBC and hemolysis to the development and progression of inflammatory pathologies are not entirely understood. In this study, we used bacterial endotoxin, lipopolysaccharide (LPS), to mimic an infectious hemolysis and found that RBCs dynamically regulated cell aggregation between immune cells and human lung microvascular endothelial cells (HLMVEC). When RBCs were treated with LPS, integrin α4β1 was increased and was accompanied by cytokines and chemokines release (TNF-α, IL-1β, IL-6, IL-8, IFN-γ, CXCL12, CCL5, CCL7 and CCL4). Upon α4β1 elevation, RBCs not only facilitated mature monocyte derived dendritic cell (mo-DCs) adhesion but also promoted HLMVEC aggregation. Furthermore, co-culture of the supernatant of LPS pre-treated RBCs with mo-DCs could promote naïve CD4 T cell proliferation. Notably, the filtered culture from LPS-lysed RBCs further promoted mo-DCs migration in a concentration dependent manner. From a therapeutic perspective, cyclic peptide inhibitor of integrin α4β1 combined with methylprednisolone (α4β1/Methrol) remarkably blocked RBCs aggregation to mo-DCs, HLMVEC, or mo-DCs and HLMVEC mixture. Moreover, α4β1/Methrol dramatically reduced mo-DCs migration up-regulated glucocorticoid-induced leucine zipper in mo-DCs, and ultimately reversed immune cell dysfunction induced by hemolysis. Taken together, these results indicate that integrin α4β1 on RBCs could mediate cell-cell interaction for adaptive immunity through influencing cell adhesion, migration, and T cell proliferation.
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spelling pubmed-80938022021-05-05 Integrin α4β1/VCAM-1 Interaction Evokes Dynamic Cell Aggregation Between Immune Cells and Human Lung Microvascular Endothelial Cells at Infectious Hemolysis Lou, Hai-Yan Yan, Hai-Peng Yang, Long-Gui Fan, Jiang-hua Cho, William C. Xiao, Zheng-hui Li, Shuang-Jie Front Pharmacol Pharmacology Bacterial and viral infection is a common cause of pneumonia, respiratory failure, and even acute respiratory distress syndrome. Increasing evidence indicates that red blood cells (RBCs) may contribute to immune response and inflammation. However, the precise molecular mechanisms that link RBC and hemolysis to the development and progression of inflammatory pathologies are not entirely understood. In this study, we used bacterial endotoxin, lipopolysaccharide (LPS), to mimic an infectious hemolysis and found that RBCs dynamically regulated cell aggregation between immune cells and human lung microvascular endothelial cells (HLMVEC). When RBCs were treated with LPS, integrin α4β1 was increased and was accompanied by cytokines and chemokines release (TNF-α, IL-1β, IL-6, IL-8, IFN-γ, CXCL12, CCL5, CCL7 and CCL4). Upon α4β1 elevation, RBCs not only facilitated mature monocyte derived dendritic cell (mo-DCs) adhesion but also promoted HLMVEC aggregation. Furthermore, co-culture of the supernatant of LPS pre-treated RBCs with mo-DCs could promote naïve CD4 T cell proliferation. Notably, the filtered culture from LPS-lysed RBCs further promoted mo-DCs migration in a concentration dependent manner. From a therapeutic perspective, cyclic peptide inhibitor of integrin α4β1 combined with methylprednisolone (α4β1/Methrol) remarkably blocked RBCs aggregation to mo-DCs, HLMVEC, or mo-DCs and HLMVEC mixture. Moreover, α4β1/Methrol dramatically reduced mo-DCs migration up-regulated glucocorticoid-induced leucine zipper in mo-DCs, and ultimately reversed immune cell dysfunction induced by hemolysis. Taken together, these results indicate that integrin α4β1 on RBCs could mediate cell-cell interaction for adaptive immunity through influencing cell adhesion, migration, and T cell proliferation. Frontiers Media S.A. 2021-04-20 /pmc/articles/PMC8093802/ /pubmed/33959020 http://dx.doi.org/10.3389/fphar.2021.653143 Text en Copyright © 2021 Lou, Yan, Yang, Fan, Cho, Xiao and Li. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Lou, Hai-Yan
Yan, Hai-Peng
Yang, Long-Gui
Fan, Jiang-hua
Cho, William C.
Xiao, Zheng-hui
Li, Shuang-Jie
Integrin α4β1/VCAM-1 Interaction Evokes Dynamic Cell Aggregation Between Immune Cells and Human Lung Microvascular Endothelial Cells at Infectious Hemolysis
title Integrin α4β1/VCAM-1 Interaction Evokes Dynamic Cell Aggregation Between Immune Cells and Human Lung Microvascular Endothelial Cells at Infectious Hemolysis
title_full Integrin α4β1/VCAM-1 Interaction Evokes Dynamic Cell Aggregation Between Immune Cells and Human Lung Microvascular Endothelial Cells at Infectious Hemolysis
title_fullStr Integrin α4β1/VCAM-1 Interaction Evokes Dynamic Cell Aggregation Between Immune Cells and Human Lung Microvascular Endothelial Cells at Infectious Hemolysis
title_full_unstemmed Integrin α4β1/VCAM-1 Interaction Evokes Dynamic Cell Aggregation Between Immune Cells and Human Lung Microvascular Endothelial Cells at Infectious Hemolysis
title_short Integrin α4β1/VCAM-1 Interaction Evokes Dynamic Cell Aggregation Between Immune Cells and Human Lung Microvascular Endothelial Cells at Infectious Hemolysis
title_sort integrin α4β1/vcam-1 interaction evokes dynamic cell aggregation between immune cells and human lung microvascular endothelial cells at infectious hemolysis
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093802/
https://www.ncbi.nlm.nih.gov/pubmed/33959020
http://dx.doi.org/10.3389/fphar.2021.653143
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