PMID- 20538801
OWN - NLM
STAT- MEDLINE
DCOM- 20101027
LR  - 20211020
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 116
IP  - 12
DP  - 2010 Sep 23
TI  - A revised model for the secretion of tPA and cytokines from cultured endothelial 
      cells.
PG  - 2183-91
LID - 10.1182/blood-2010-03-276170 [doi]
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-1beta (IL-1beta), the cytokines IL-8, IL-6, 
      monocyte chemoattractant protein-1 (MCP-1), and growth-regulated oncogene-alpha 
      (GRO-alpha). 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-1beta-treated cells, IL-8, IL-6, MCP-1, and 
      GRO-alpha, 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.
FAU - Knipe, Laura
AU  - Knipe L
AD  - Medical Research Council, National Institute for Medical Research, London, UK.
FAU - Meli, Athinoula
AU  - Meli A
FAU - Hewlett, Lindsay
AU  - Hewlett L
FAU - Bierings, Ruben
AU  - Bierings R
FAU - Dempster, John
AU  - Dempster J
FAU - Skehel, Paul
AU  - Skehel P
FAU - Hannah, Matthew J
AU  - Hannah MJ
FAU - Carter, Tom
AU  - Carter T
LA  - eng
GR  - MC_U117573808/MRC_/Medical Research Council/United Kingdom
GR  - U117573808/MRC_/Medical Research Council/United Kingdom
GR  - U117570589/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100610
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Cytokines)
RN  - EC 3.4.21.68 (Tissue Plasminogen Activator)
SB  - IM
MH  - Cell Compartmentation
MH  - Cells, Cultured
MH  - Cytokines/*metabolism
MH  - Endothelial Cells/*metabolism
MH  - Endothelium, Vascular/*cytology
MH  - Humans
MH  - Models, Biological
MH  - Tissue Plasminogen Activator/*metabolism
MH  - Weibel-Palade Bodies/metabolism
PMC - PMC2951859
EDAT- 2010/06/12 06:00
MHDA- 2010/10/28 06:00
PMCR- 2010/09/23
CRDT- 2010/06/12 06:00
PHST- 2010/06/12 06:00 [entrez]
PHST- 2010/06/12 06:00 [pubmed]
PHST- 2010/10/28 06:00 [medline]
PHST- 2010/09/23 00:00 [pmc-release]
AID - S0006-4971(20)32970-0 [pii]
AID - 2010/276170 [pii]
AID - 10.1182/blood-2010-03-276170 [doi]
PST - ppublish
SO  - Blood. 2010 Sep 23;116(12):2183-91. doi: 10.1182/blood-2010-03-276170. Epub 2010 
      Jun 10.