Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1996-7-18
pubmed:abstractText
In contrast to normal microvessels, those that supply tumors are strikingly hyperpermeable to circulating macromolecules such as plasma proteins. This leakiness is largely attributable to a tumor-secreted cytokine, vascular permeability factor (VPF). Tracer studies have shown that macromolecules cross tumor vascular endothelium by way of a recently described cytoplasmic organelle, the vesiculo-vacuolar organelle or VVO (VVOs are grapelike clusters of interconnected, uncoated vesicles and vacuoles). However, equivalent VVOs are also present in the cytoplasm of normal venules that do not leak substantial amounts of plasma protein. To explain these findings, we hypothesized that VPF increased the permeability of tumor blood vessels by increasing VVO function and that the VVOs of normal venules were relatively impermeable in the absence of VPF stimulation. To test this hypothesis, VPF was injected intradermally in normal animals after intravenous injection of a soluble macromolecular tracer, ferritin, whose extravasation could be followed by electron microscopy. VPF caused normal venules to leak ferritin, and, as predicted by our hypothesis, ferritin extravasated by way of VVOs, just as in hyperpermeable tumor microvessels. Ultrathin (14-nm) serial electron microscopic sections and computer-aided three-dimensional reconstructions better defined VVO structure. VVOs occupied 16-18% of endothelial cytoplasm in normal venules. Individual VVOs were clusters of numerous (median, 124) interconnected vesicles and vacuoles that formed complex pathways across venular endothelium with multiple openings to both luminal and abluminal surfaces. Like VPF, histamine and serotonin also stimulated ferritin extravasation across venules by way of VVOs. Together, these data establish VVOs as the major pathway by which soluble plasma proteins exit venules in response to several mediators that increase venular hyperpermeability. These same mediators also increased the extravasation of colloidal carbon, but this large particulate nonphysiological tracer exited venules primarily through endothelial gaps.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/8642308-1279271, http://linkedlifedata.com/resource/pubmed/commentcorrection/8642308-14468626, http://linkedlifedata.com/resource/pubmed/commentcorrection/8642308-1563597, http://linkedlifedata.com/resource/pubmed/commentcorrection/8642308-1795183, http://linkedlifedata.com/resource/pubmed/commentcorrection/8642308-2057577, http://linkedlifedata.com/resource/pubmed/commentcorrection/8642308-2260625, http://linkedlifedata.com/resource/pubmed/commentcorrection/8642308-2292138, http://linkedlifedata.com/resource/pubmed/commentcorrection/8642308-3075669, http://linkedlifedata.com/resource/pubmed/commentcorrection/8642308-529011, http://linkedlifedata.com/resource/pubmed/commentcorrection/8642308-5801425, http://linkedlifedata.com/resource/pubmed/commentcorrection/8642308-6318239, http://linkedlifedata.com/resource/pubmed/commentcorrection/8642308-6823562, http://linkedlifedata.com/resource/pubmed/commentcorrection/8642308-6996584, http://linkedlifedata.com/resource/pubmed/commentcorrection/8642308-7534783, http://linkedlifedata.com/resource/pubmed/commentcorrection/8642308-7538264, http://linkedlifedata.com/resource/pubmed/commentcorrection/8642308-7673356, http://linkedlifedata.com/resource/pubmed/commentcorrection/8642308-8295933, http://linkedlifedata.com/resource/pubmed/commentcorrection/8642308-8558058
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-1007
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
183
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1981-6
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed-meshheading:8642308-Animals, pubmed-meshheading:8642308-Capillary Permeability, pubmed-meshheading:8642308-Computer Simulation, pubmed-meshheading:8642308-Endothelial Growth Factors, pubmed-meshheading:8642308-Endothelium, Vascular, pubmed-meshheading:8642308-Female, pubmed-meshheading:8642308-Ferritins, pubmed-meshheading:8642308-Guinea Pigs, pubmed-meshheading:8642308-Histamine, pubmed-meshheading:8642308-Humans, pubmed-meshheading:8642308-Lymphokines, pubmed-meshheading:8642308-Male, pubmed-meshheading:8642308-Microscopy, Electron, pubmed-meshheading:8642308-Models, Structural, pubmed-meshheading:8642308-Organelles, pubmed-meshheading:8642308-Rats, pubmed-meshheading:8642308-Rats, Sprague-Dawley, pubmed-meshheading:8642308-Recombinant Proteins, pubmed-meshheading:8642308-Serotonin, pubmed-meshheading:8642308-Skin, pubmed-meshheading:8642308-Vacuoles, pubmed-meshheading:8642308-Vascular Endothelial Growth Factor A, pubmed-meshheading:8642308-Vascular Endothelial Growth Factors, pubmed-meshheading:8642308-Venules
pubmed:year
1996
pubmed:articleTitle
Vesiculo-vacuolar organelles and the regulation of venule permeability to macromolecules by vascular permeability factor, histamine, and serotonin.
pubmed:affiliation
Department of Pathology, Beth Israel Hospital, Boston, Massachusetts 02215, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't