title: Decrease in the amount of focal adhesion kinase (p125(FAK)) in interleukin-1beta-stimulated human umbilical vein endothelial cells by binding of human monocytic cell lines.
abstract: Monocytes in the blood circulation migrate across endothelial cell monolayers lining the blood vessels and infiltrate into the underlying tissues in inflammation. However, little is known about the mechanisms by which leukocytes migrate across the endothelial barrier after binding and what molecules participate in the process. Addition of the human monocytic cell line THP-1 to interleukin-1beta (IL-1beta)-stimulated human umbilical vein endothelial cells (HUVEC) induced a decrease in the amount of focal adhesion kinase (p125(FAK)) protein, a tyrosine kinase localized at focal contacts and essential for cell attachment to the extracellular matrix, whereas little change was observed in the amount of other molecules associated with cell adhesion such as vascular cell adhesion molecule-1, alpha-catenin, and talin. A maximum decrease 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 recovered. A reduction in the density of actin stress fibers in IL-1beta-activated HUVEC was observed in parallel with the decrease in p125(FAK). The p125(FAK) decrease was partially 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 monocytes in inflammation facilitates the transendothelial migration of the monocytes by altering the adhesiveness of endothelial cells to the extracellular matrix.
authors.affiliation: Fujisaki Institute, Hayashibara Biochemical Laboratories, Inc., 675-1 Fujisaki, Okayama 702, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Iwaki
authors.forename: K
authors.initials: K
authors.lastname: Ohashi
authors.forename: M
authors.initials: M
authors.lastname: Ikeda
authors.forename: K
authors.initials: K
authors.lastname: Tsujioka
authors.forename: F
authors.initials: F
authors.lastname: Kajiya
authors.forename: M
authors.initials: M
authors.lastname: Kurimoto
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000032:analysis*; D002460:Cell Line; D018920:Coculture Techniques; D003599:Cytoskeleton / Q000737:chemistry; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D009000:Monocytes / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000032:analysis*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins
chemical_list: D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human