Monocytic microparticles activate endothelial cells in an IL-1β–dependent manner

• Published in: Blood 2011-08, Vol.118 (8), p.2366-2374
• Main Authors: Wang, Jian-Guo, Williams, Julie C., Davis, Beckley K., Jacobson, Ken, Doerschuk, Claire M., Ting, Jenny P.-Y., Mackman, Nigel
• Format: Article
• Language: English
• Subjects: 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
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2011-01-330878

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.