CYTOKINE-INDUCED INCREASES IN ENDOTHELIAL PERMEABILITY OCCUR AFTER ADHESION MOLECULE EXPRESSION

Background. Transmigration of neutrophils (PMNs) through endothelial c ell tight junctions is a critical stage in the tissue injury of ischem ia-reperfusion (I/R). Although cytokines are released in I/R, it is un clear whether cytokines directly increase permeability or this phenome non requires both expression of cell adhesion molecules and PMN adhesi on-activation. Methods. We exposed confluent monolayers of human umbil ical vein endothelial cells to physiologic concentrations of interleuk in-1 (10 pg/ml) and tumor necrosis factor-alpha (10 pg/ml) in the abse nce of PMNs. Tight junction permeability was quantified with both tran sendothelial electrical resistance and albumin flux, whereas expressio n of endothelial-leukocyte adhesion molecule-1 was measured by flow cy tometry (t test p < 0.05). Results. Simulation with tumor necrosis fac tor-alpha or interleukin-1 produced maximal transendothelial electrica l 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 endo thelial-leukocyte adhesion molecular-1 at 4 hours. Conclusions. Cytoki nes induced increased in both cell adhesion molecule expression and en dothelial permeability. This sequence of events is consistent with dir ect cytokine effects on cytoarchitecture, because is occurred without the adhesion-activation of PMNs.