LOCALIZATION OF 7H6 TIGHT JUNCTION-ASSOCIATED ANTIGEN ALONG THE CELL BORDER OF VASCULAR ENDOTHELIAL-CELLS CORRELATES WITH PARACELLULAR BARRIER FUNCTION AGAINST IONS, LARGE MOLECULES, AND CANCER-CELLS

To study the regulation of the endothelial barrier, we examined the re lationship between the paracellular barrier function and the expressio n of 7H6 antigen localized at tight junctions of endothelial cells by using transendothelial electrical resistance (TER), fluxes of albumin and dextran, transmigration of rat mammary cancer (SST-2) cells across rat lung endothelial (RLE) cells, and immunocytochemical expression o f 7H6 antigen as parameters. RLE cells cultured at a confluent cell de nsity did not express immunohistochemically demonstrable 7H6 antigen a nd had low paracellular barrier functions. However, treatment of the e ndothelial cells with 0.5 mM dibutyryl-cAMP or 10(-6) M all-trans-reti noic acid for 4 days induced 7H6 antigen preferentially at the cell bo rder and simultaneously enhanced the barrier function twofold, in term s of TER and fluxes of albumin and dextran. Furthermore, RA-treated RL E cell monolayers with the enhanced barrier function significantly inh ibited the transmigration of SST-2 cells. These results together with those of our previous study indicate that 7H6 antigen has a crucial ro le in the regulation of paracellular barrier function not only in epit helial cells but also in vascular endothelial cells. The present study also suggests that tight junctions of vascular endothelium in vivo fu nction as a barrier between blood and tissues against metastatic cance r cells. (C) 1996 Academic Press, Inc.