Tumor necrosis factor enhances the neutrophil‐dependent increase in endothelial permeability

Publisher Website
Google Scholar
Abstract
We examined the effect of tumor necrosis factor α (TNFα) on the increase in pulmonary microvascular endothelial monolayer permeability induced by activated neutrophils (PMN). Layering of PMN onto endothelial monolayers followed by activation of PMN with phorbol 12-myristate 13-acetate (PMA) increased 125I-albumin clearance rate across the monolayers. Pretreatment of endothelial monolayers for 6 hr with TNFα (200 U/ml) potentiated the PMN-dependent increase in endothelial permeability, whereas 1 hr or 6 hr pretreatment of endothelial monolayers with 200 U/ml and 100 U/ml, respectively, TNFα did not enhance the reponse. Adherence of PMN to the endothelial cells was increased at 1 and 6 hr after TNFα (200 U/ml) treatment, but the adherence reponse was markedly greater following 6 hr of TNFα. The TNFα treatment of endothelial cells did not enhance neutrophil activation responses to PMA. Pretmeatment of PMN with IB4, a MAb to the CD18 integrin, the common β subunit of the adhesion proteins LFA-1, Mac-1, and p150,95 of PMN, reduced the increases in PMN adherence and the endothelial monolayer permeability induced by the 6 hr TNFα treatment. In contrast, pretreatment of PMN with OKM-1, a MAb to the CD11b epitope (-subunit), had no effect on the adherence and the potentiation of the increase in permeability. The potentiation of the PMN-dependent permeability increase and enhanced endothelial adhesivity at 6 hr after TNFα priming of endothelial cells was dependent on protein synthesis. The results indicate that protein synthesis-dependent expression of an endothelial ligand for CD18 and resultant endothelial hyperadhesiveness potentiates the PMN-mediated increase in endothelial permeability after TNFα activation of endothelial cells. The priming of endothelial cells by TNFα may be a critical step in the mediation of endothelial injury.