Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1996-2-13
pubmed:abstractText
Hemolytic uremic syndrome (HUS), which is the most common cause of acute renal failure in infants and small children, is caused by verotoxin (VT)-producing Escherichia coli infection. Endothelial injury determines microvascular thrombosis and evidence is available from recent studies that suggests that leukocyte activation participates in endothelial damage. We studied here the effect of VT-1 on leukocyte adhesion to vascular endothelium under physiologic flow conditions. Human umbilical vein endothelial cells (HUVECs) were incubated for 24 hours with VT-1 (0.1, 1, and 10 pmol/L) and then exposed to a total leukocyte suspension in a parallel plate flow chamber under laminar flow conditions (1.5 dynes/cm2). Adherent cells were counted by digital image processing. Results showed that VT-1 dose-dependently increased the number of adhering leukocytes to HUVECs as compared with unstimulated cells. The adhesive response elicited by VT-1 was comparable to that of interleukin-1 beta (IL-1 beta), one of the most potent inducers of endothelial cell adhesiveness. Exposure of HUVECs to VT-1 did not affect the number of rolling leukocytes, which was similar to that of control values. To examine the role of adhesion molecules in VT-1-induced leukocyte adhesion, HUVECs were incubated with mouse monoclonal antibodies against E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) before adhesion assay. Functional blocking of E-selectin, ICAM-1, and VCAM-1 on endothelial cells significantly inhibited VT-1-induced increase in leukocyte adhesion. In some experiments, before VT-1 incubation, HUVECs were pretreated for 24 hours with tumor necrosis factor alpha (TNF alpha; 100 U/mL), which is known to increase VT receptor expression on HUVECs. The number of adhering leukocytes on HUVECs exposed to TNF alpha and VT-1 significantly increased as compared with HUVECs incubated with VT-1 and TNF alpha alone. These results suggest that VT-1 modulates leukocyte-endothelium interaction, thus increasing leukocyte adhesion and upregulating adhesive proteins on endothelial surface membrane.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
86
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4553-8
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:8541545-Animals, pubmed-meshheading:8541545-Antibodies, Monoclonal, pubmed-meshheading:8541545-Bacterial Toxins, pubmed-meshheading:8541545-Cell Adhesion, pubmed-meshheading:8541545-Cells, Cultured, pubmed-meshheading:8541545-Chemotaxis, Leukocyte, pubmed-meshheading:8541545-Child, pubmed-meshheading:8541545-E-Selectin, pubmed-meshheading:8541545-Endothelium, Vascular, pubmed-meshheading:8541545-Hemolytic-Uremic Syndrome, pubmed-meshheading:8541545-Hemorheology, pubmed-meshheading:8541545-Humans, pubmed-meshheading:8541545-Intercellular Adhesion Molecule-1, pubmed-meshheading:8541545-Interleukin-1, pubmed-meshheading:8541545-Kidney, pubmed-meshheading:8541545-Leukocytes, pubmed-meshheading:8541545-Mice, pubmed-meshheading:8541545-Microcirculation, pubmed-meshheading:8541545-Renal Circulation, pubmed-meshheading:8541545-Shiga Toxin 1, pubmed-meshheading:8541545-Stimulation, Chemical, pubmed-meshheading:8541545-Tumor Necrosis Factor-alpha, pubmed-meshheading:8541545-Umbilical Veins, pubmed-meshheading:8541545-Up-Regulation, pubmed-meshheading:8541545-Vascular Cell Adhesion Molecule-1
pubmed:year
1995
pubmed:articleTitle
Verotoxin-1 promotes leukocyte adhesion to cultured endothelial cells under physiologic flow conditions.
pubmed:affiliation
Mario Negri Institute for Pharmacological Research, Bergamo, Italy.
pubmed:publicationType
Journal Article