DECREASE IN THE AMOUNT OF FOCAL ADHESION KINASE (P125(FAK)) IN INTERLEUKIN-1-BETA-STIMULATED HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS BY BINDING OF HUMAN MONOCYTIC CELL-LINES

Monocytes in the blood circulation migrate across endothelial cell mon olayers lining the blood vessels and infiltrate into the underlying ti ssues in inflammation, However, little is known about the mechanisms b y which leukocytes migrate across the endothelial barrier after bindin g and what molecules participate in the process, Addition of the human monocytic cell line THP-1 to interleukin-1 beta (IL-1 beta)-stimulate d human umbilical vein endothelial cells (HUVEC) induced a decrease in the amount of focal adhesion kinase (p125(FAK)) protein, a tyrosine k inase localized at focal contacts and essential for cell attachment to the extracellular matrix, whereas little change was observed in the a mount of other molecules associated with cell adhesion such as vascula r cell adhesion molecule-1, alpha-catenin, and talin, A maximum decrea se in the amount of p125(FAK) was observed 15-30 min after addition of THP-1 cells to HUVEC, after which the level of p125(FAK) gradually re covered, A reduction in the density of actin stress fibers in IL-1 bet a-activated HUVEC was observed in parallel with the decrease in p125FA K. The p125(FAK) decrease was par tially inhibited by preventing THP-1 binding to HUVEC using a mixture of antibodies to adhesion molecules, We suggest that the decrease in p125(FAK) triggered by binding of mon ocytes in inflammation facilitates the transendothelial migration of t he monocytes by altering the adhesiveness of endothelial cells to the extracellular matrix.