期刊
BLOOD
卷 118, 期 8, 页码 2366-2374出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2011-01-330878
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资金
- National Institutes of Health [HL-066350]
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-kappa B 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-1 beta 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-1 beta and may amplify inflammation by enhancing the activation of the endothelium. (Blood. 2011; 118(8): 2366-2374)
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