Monocytic microparticles activate endothelial cells in an IL-1β–dependent manner
Microparticles (MPs) are shed from activated and dying cells. They can transmit signals from cell to cell, locally or at a distance through the circulation. Monocytic MPs are elevated in different diseases, including bacterial infections. Here, we investigated how monocytic MPs activate endothelial...
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Published in | Blood Vol. 118; no. 8; pp. 2366 - 2374 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
Washington, DC
Elsevier Inc
25.08.2011
Americain Society of Hematology American Society of Hematology |
Subjects | |
Online Access | Get full text |
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Abstract | Microparticles (MPs) are shed from activated and dying cells. They can transmit signals from cell to cell, locally or at a distance through the circulation. Monocytic MPs are elevated in different diseases, including bacterial infections. Here, we investigated how monocytic MPs activate endothelial cells. We found that MPs from lipopolysaccharide (LPS)–treated THP-1 monocytic cells bind to and are internalized by human endothelial cells. MPs from LPS-treated THP-1 cells, but not untreated cells, induced phosphorylation of ERK1/2, activation of the nuclear factor-κB pathway and expression of cell adhesion molecules intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin. Similar results were observed using MPs from LPS-treated peripheral blood mononuclear cells. We next investigated the mechanism by which monocytic MPs activated endothelial cells and found that they contain IL-1β and components of the inflammasome, including apoptosis-associated speck-like protein containing a CARD, caspase-1, and NLRP3. Importantly, knockdown of NLRP3 in THP-1 cells reduced the activity of the MPs and blockade of the IL-1 receptor on endothelial cells decreased MP-dependent induction of cell adhesion molecules. Therefore, monocytic MPs contain IL-1β and may amplify inflammation by enhancing the activation of the endothelium. |
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AbstractList | Microparticles (MPs) are shed from activated and dying cells. They can transmit signals from cell to cell, locally or at a distance through the circulation. Monocytic MPs are elevated in different diseases, including bacterial infections. Here, we investigated how monocytic MPs activate endothelial cells. We found that MPs from lipopolysaccharide (LPS)–treated THP-1 monocytic cells bind to and are internalized by human endothelial cells. MPs from LPS-treated THP-1 cells, but not untreated cells, induced phosphorylation of ERK1/2, activation of the nuclear factor-κB pathway and expression of cell adhesion molecules intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin. Similar results were observed using MPs from LPS-treated peripheral blood mononuclear cells. We next investigated the mechanism by which monocytic MPs activated endothelial cells and found that they contain IL-1β and components of the inflammasome, including apoptosis-associated speck-like protein containing a CARD, caspase-1, and NLRP3. Importantly, knockdown of NLRP3 in THP-1 cells reduced the activity of the MPs and blockade of the IL-1 receptor on endothelial cells decreased MP-dependent induction of cell adhesion molecules. Therefore, monocytic MPs contain IL-1β and may amplify inflammation by enhancing the activation of the endothelium. |
Author | Doerschuk, Claire M. Mackman, Nigel Williams, Julie C. Ting, Jenny P.-Y. Jacobson, Ken Davis, Beckley K. Wang, Jian-Guo |
Author_xml | – sequence: 1 givenname: Jian-Guo surname: Wang fullname: Wang, Jian-Guo organization: Division of Hematology and Oncology, Department of Medicine, McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC – sequence: 2 givenname: Julie C. surname: Williams fullname: Williams, Julie C. organization: Division of Hematology and Oncology, Department of Medicine, McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC – sequence: 3 givenname: Beckley K. surname: Davis fullname: Davis, Beckley K. organization: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC – sequence: 4 givenname: Ken surname: Jacobson fullname: Jacobson, Ken organization: Department of Cell and Developmental Biology, University of North Carolina at Chapel Hill, Chapel Hill, NC – sequence: 5 givenname: Claire M. surname: Doerschuk fullname: Doerschuk, Claire M. organization: Department of Medicine, Center for Airways Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC – sequence: 6 givenname: Jenny P.-Y. surname: Ting fullname: Ting, Jenny P.-Y. organization: Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC – sequence: 7 givenname: Nigel surname: Mackman fullname: Mackman, Nigel email: nmackman@med.unc.edu organization: Division of Hematology and Oncology, Department of Medicine, McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC |
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Copyright | 2011 American Society of Hematology 2015 INIST-CNRS 2011 by The American Society of Hematology 2011 |
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Keywords | Interleukin 1β Microparticle Endothelial cell Hematology Monocyte Cytokine |
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Notes | J.-G.W. and J.C.W. contributed equally to this study. |
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Snippet | Microparticles (MPs) are shed from activated and dying cells. They can transmit signals from cell to cell, locally or at a distance through the circulation.... |
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SubjectTerms | Biological and medical sciences Carrier Proteins - antagonists & inhibitors Carrier Proteins - genetics Cell Adhesion Molecules - physiology Cell Line Cell-Derived Microparticles - drug effects Cell-Derived Microparticles - physiology Cells, Cultured Endothelial Cells - physiology Gene Knockdown Techniques Hematologic and hematopoietic diseases Humans Inflammasomes - physiology Inflammation Mediators - physiology Interleukin 1 Receptor Antagonist Protein - pharmacology Interleukin-1beta - physiology Lipopolysaccharides - toxicity Medical sciences Monocytes - drug effects Monocytes - physiology NLR Family, Pyrin Domain-Containing 3 Protein Phagocytes, Granulocytes, and Myelopoiesis Receptors, Interleukin-1 - antagonists & inhibitors Signal Transduction Vascular Biology |
Title | Monocytic microparticles activate endothelial cells in an IL-1β–dependent manner |
URI | https://dx.doi.org/10.1182/blood-2011-01-330878 https://www.ncbi.nlm.nih.gov/pubmed/21700772 https://pubmed.ncbi.nlm.nih.gov/PMC3162361 |
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