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A revised model for the secretion of tPA and cytokines from cultured endothelial cells.

Knipe, L; Meli, A; Hewlett, L; Bierings, R; Dempster, J; Skehel, P; Hannah, MJ; Carter, T (2010) A revised model for the secretion of tPA and cytokines from cultured endothelial cells. Blood, 116 (12). pp. 2183-2191. ISSN 0006-4971 https://doi.org/10.1182/blood-2010-03-276170
SGUL Authors: Carter, Thomas David

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Abstract

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.

Item Type: Article
Additional Information: © 2010 by The American Society of Hematology. Published version made available with permission of publisher.
Keywords: Cell Compartmentation, Cells, Cultured, Cytokines, Endothelial Cells, Endothelium, Vascular, Humans, Models, Biological, Tissue Plasminogen Activator, Weibel-Palade Bodies, Endothelium, Vascular, Cells, Cultured, Weibel-Palade Bodies, Endothelial Cells, Humans, Tissue Plasminogen Activator, Cytokines, Cell Compartmentation, Models, Biological, Science & Technology, Life Sciences & Biomedicine, Hematology, HEMATOLOGY, WEIBEL-PALADE BODIES, VON-WILLEBRAND-FACTOR, PLASMINOGEN-ACTIVATOR, REGULATED SECRETION, STORAGE GRANULE, IN-VITRO, T-PA, MEMBRANE, PROTEINS, RELEASE, Immunology, 1102 Cardiovascular Medicine And Haematology, 1103 Clinical Sciences, 1114 Paediatrics And Reproductive Medicine
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Cell Sciences (INCCCS)
Journal or Publication Title: Blood
ISSN: 0006-4971
Language: eng
Dates:
DateEvent
10 June 2010Published
Publisher License: Publisher's own licence
Projects:
Project IDFunderFunder ID
MC_U117573808Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
U117570589Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
U117573808Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
PubMed ID: 20538801
Web of Science ID: WOS:000282137300028
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/107676
Publisher's version: https://doi.org/10.1182/blood-2010-03-276170

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