PROLONGED CYTOKINE EXPOSURE CAUSES A DYNAMIC REDISTRIBUTION OF ENDOTHELIAL-CELL ADHESION MOLECULES TO INTERCELLULAR-JUNCTIONS

After 4 hours of treatment with TNF, newly synthesized endothelial leu kocyte adhesion molecule 1, vascular cell adhesion molecule 1, and int ercellular adhesion molecule 1 molecules are diffusely expressed on th e apical surface of cultured umbilical vein endothelial cells. Such ce lls maintain the epithelioid, cobblestone appearance of untreated endo thelial cells and display cytoskeletal actin largely arranged in dense peripheral bands. After 24 to 72 hours of treatment with TNF, cells b ecome elongated and rearrange their actin filaments into longitudinal stress fibers. At this time, intercellular adhesion molecule 1 and vas cular cell adhesion molecule 1 remain elevated but redistribute to the cell junctions. Intercellular adhesion molecule 2, beta(1) integrins, and beta(3) integrins also redistribute to cell junctions in TNF-trea ted cultures. IFN-gamma produces morphologic changes similar to those induced by TNF but does not cause surface protein redistribution. Cell s treated with TNF plus IFN-gamma become even more elongated and displ ay TNF-like redistributions. We conclude that TNF activates a program of membrane protein redistribution, and we speculate that this dynamic redistribution of adhesion molecules to cell junctions may contribute to the recruitment of leukocytes to sites of inflammation.