Cytokine-induced increases in endothelial permeability occur after adhesion molecule expression.
BACKGROUND
Transmigration of neutrophils (PMNs) through endothelial cell tight junctions is a critical stage in the tissue injury of ischemia-reperfusion (I/R). Although cytokines are released in I/R, it is unclear whether cytokines directly increase permeability or this phenomenon requires both expression of cell adhesion molecules and PMN adhesion-activation.


METHODS
We exposed confluent monolayers of human umbilical vein endothelial cells to physiologic concentrations of interleukin-1 (10 pg/ml) and tumor necrosis factor-alpha (10 pg/ml) in the absence of PMNs. Tight junction permeability was quantified with both transendothelial electrical resistance and albumin flux, whereas expression of endothelial-leukocyte adhesion molecule-1 was measured by flow cytometry (t test p < 0.05).


RESULTS
Stimulation with tumor necrosis factor-alpha or interleukin-1 produced maximal transendothelial electrical resistance decreases at 12 hours with return to baseline at 24 hours. Increases in albumin flux began at 6 hours, with maximum effects at 24 hours. These changes occurred soon after maximal expression of endothelial-leukocyte adhesion molecule-1 at 4 hours.


CONCLUSIONS
Cytokines induced increases in both cell adhesion molecule expression and endothelial permeability. This sequence of events is consistent with direct cytokine effects on cytoarchitecture, because it occurred without the adhesion-activation of PMNs.
Marcus
B C
BC
Department of Surgery, University of Chicago-Pritzker School of Medicine, Ill., USA.
Wyble
C W
CW
Hynes
K L
KL
Gewertz
B L
BL
D000418:Albumins / Q000493:pharmacokinetics*; D002463:Cell Membrane Permeability / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured / Q000378:metabolism; D015638:Cytochalasin D / Q000494:pharmacology; D019040:E-Selectin / Q000096:biosynthesis*; D017097:Electric Impedance; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D019108:Tight Junctions / Q000187:drug effects / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology
D000418:Albumins; D019040:E-Selectin; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D015638:Cytochalasin D