Abstract
| Language | English |
|---|---|
| Pages | 2183-2191 |
| Number of pages | 9 |
| Journal | Blood |
| Volume | 116 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 23 Sep 2010 |
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Keywords
- cell compartmentation
- cells, cultured
- cytokines
- endothelial cells
- endothelium, vascular
- humans
- models, biological
- tissue plasminogen activator
- Weibel-Palade bodies
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A revised model for the secretion of tPA and cytokines from cultured endothelial cells. / Knipe, Laura; Meli, Athinoula; Hewlett, Lindsay; Bierings, Ruben; Dempster, John; Skehel, Paul; Hannah, Matthew J; Carter, Tom.
In: Blood, Vol. 116, No. 12, 23.09.2010, p. 2183-2191.Research output: Contribution to journal › Article
TY - JOUR
T1 - A revised model for the secretion of tPA and cytokines from cultured endothelial cells
AU - Knipe, Laura
AU - Meli, Athinoula
AU - Hewlett, Lindsay
AU - Bierings, Ruben
AU - Dempster, John
AU - Skehel, Paul
AU - Hannah, Matthew J
AU - Carter, Tom
PY - 2010/9/23
Y1 - 2010/9/23
N2 - Endothelial cells are reported to contain several distinct populations of regulated secretory organelles, including Weibel-Palade bodies (WPBs), the tissue plasminogen activator (tPA) organelle, and the type-2 chemokine-containing organelle. We show that the tPA and type-2 organelles in human endothelial cells represent a single compartment primarily responsible for unstimulated secretion of tPA or, in cells exposed to interleukin-1β (IL-1β), the cytokines IL-8, IL-6, monocyte chemoattractant protein-1 (MCP-1), and growth-regulated oncogene-α (GRO-α). This compartment was distinct from WPBs in that it lacked detectable von Willebrand factor, P-selectin, Rab27a, or CD63 immunoreactivity, displayed no time-dependent decrease in intragranule pH, underwent detectable unstimulated exocytosis, and was very poorly responsive to Ca(2+)-elevating secretagogues. WPBs could also contain tPA, and in IL-1β-treated cells, IL-8, IL-6, MCP-1, and GRO-α, and were the primary source for histamine or ionomycin-stimulated secretion of these molecules. However, analysis of the storage efficiency of cytokines and tPA revealed that all were very poorly stored compared with von Willebrand factor. The nonmammalian, nonsecretory protein EGFP, when expressed in the secretory pathway, also entered WPBs and had a storage efficiency similar to tPA and the cytokines tested. Based on these data, we proposed a revised model for storage and secretion of cytokines and tPA.
AB - Endothelial cells are reported to contain several distinct populations of regulated secretory organelles, including Weibel-Palade bodies (WPBs), the tissue plasminogen activator (tPA) organelle, and the type-2 chemokine-containing organelle. We show that the tPA and type-2 organelles in human endothelial cells represent a single compartment primarily responsible for unstimulated secretion of tPA or, in cells exposed to interleukin-1β (IL-1β), the cytokines IL-8, IL-6, monocyte chemoattractant protein-1 (MCP-1), and growth-regulated oncogene-α (GRO-α). This compartment was distinct from WPBs in that it lacked detectable von Willebrand factor, P-selectin, Rab27a, or CD63 immunoreactivity, displayed no time-dependent decrease in intragranule pH, underwent detectable unstimulated exocytosis, and was very poorly responsive to Ca(2+)-elevating secretagogues. WPBs could also contain tPA, and in IL-1β-treated cells, IL-8, IL-6, MCP-1, and GRO-α, and were the primary source for histamine or ionomycin-stimulated secretion of these molecules. However, analysis of the storage efficiency of cytokines and tPA revealed that all were very poorly stored compared with von Willebrand factor. The nonmammalian, nonsecretory protein EGFP, when expressed in the secretory pathway, also entered WPBs and had a storage efficiency similar to tPA and the cytokines tested. Based on these data, we proposed a revised model for storage and secretion of cytokines and tPA.
KW - cell compartmentation
KW - cells, cultured
KW - cytokines
KW - endothelial cells
KW - endothelium, vascular
KW - humans
KW - models, biological
KW - tissue plasminogen activator
KW - Weibel-Palade bodies
U2 - 10.1182/blood-2010-03-276170
DO - 10.1182/blood-2010-03-276170
M3 - Article
VL - 116
SP - 2183
EP - 2191
JO - Blood
T2 - Blood
JF - Blood
SN - 0006-4971
IS - 12
ER -