title: Monocytic microparticles activate endothelial cells in an IL-1β-dependent manner.
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.
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, McAllister Heart Institute, Chapel Hill, NC, USA.
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Wang
authors.forename: Julie C
authors.initials: JC
authors.lastname: Williams
authors.forename: Beckley K
authors.initials: BK
authors.lastname: Davis
authors.forename: Ken
authors.initials: K
authors.lastname: Jacobson
authors.forename: Claire M
authors.initials: CM
authors.lastname: Doerschuk
authors.forename: Jenny P-Y
authors.initials: JP
authors.lastname: Ting
authors.forename: Nigel
authors.initials: N
authors.lastname: Mackman
mesh_terms: D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000502:physiology; D002460:Cell Line; D055252:Cell-Derived Microparticles / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006801:Humans; D058847:Inflammasomes / Q000502:physiology; D018836:Inflammation Mediators / Q000502:physiology; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology; D053583:Interleukin-1beta / Q000502:physiology*; D008070:Lipopolysaccharides / Q000633:toxicity; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D015398:Signal Transduction
chemical_list: D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D058847:Inflammasomes; D018836:Inflammation Mediators; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D017472:Receptors, Interleukin-1