The role of the microtubules in tumor necrosis factor-α-induced endothelial cell permeability

Tumor necrosis factor (TNF)-α, a major proinflammatory cytokine, triggers endothelial cell activation and barrier dysfunction which are implicated in the pathogenesis of pulmonary edema associated with acute lung injury syndromes. The mechanisms of TNF-α–induced vascular permeability are not completely understood. Our initial experiments demonstrated that TNF-α–induced decreases in transendothelial electrical resistance across human pulmonary artery endothelial cells are independent of myosin light chain phosphorylation catalyzed by either myosin light chain kinase or Rho kinase. We next assessed the involvement of another cytoskeletal component, the tubulin-based microtubule network, and found TNF-α to induce a decrease in stable tubulin content and partial dissolution of peripheral microtubule network as evidenced by anti-acetylated tubulin and anti–β-tubulin immunofluorescent staining, respectively. Microtubule-stabilizing agents, paclitaxel and epothilone B, significantly attenuated TNF-α–induced decr...