Attenuation of human leukocyte adherence to endothelial cell monolayers by tyrosine kinase inhibitors.
Expression of cell adhesion molecules is controlled by various cytokines including interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF alpha), but the underlying mechanisms are not clear. In this study, we investigated the role of tyrosine phosphorylated proteins in the regulation of leukocyte adhesion to endothelial cells. We examined the effect of genistein and herbimycin-A, selective inhibitors of tyrosine kinase, on the adherence of human blood neutrophils, lymphocytes, and monocytes to monolayers of human umbilical vein endothelial cells. Both genistein and herbimycin A significantly inhibited IL-1 and TNF alpha-induced upregulation of neutrophils (p < 0.05) and monocyte (p < 0.01) adherence. IL-1 and TNF alpha-stimulated lymphocyte adherence was diminished in the presence of herbimycin A (p < 0.05), but genistein only inhibited TNF alpha-stimulated adherence. There was no significant effect of genistein on IL-1-induced lymphocyte adherence. These novel findings reveal for the first time that tyrosine phosphorylated proteins may regulate leukocyte adherence and cell adhesion molecule expression on the endothelium.
McGregor
P E
PE
Department of Surgery, Creighton University School of Medicine, Omaha, NE 68178.
Agrawal
D K
DK
Edwards
J D
JD
D000704:Analysis of Variance; D016227:Benzoquinones; D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D019833:Genistein; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007529:Isoflavones / Q000494:pharmacology*; D047029:Lactams, Macrocyclic; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology*; D008214:Lymphocytes / Q000187:drug effects / Q000502:physiology; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D010750:Phosphoproteins / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011809:Quinones / Q000494:pharmacology*; D017828:Rifabutin / Q000031:analogs & derivatives; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins
D016227:Benzoquinones; D007375:Interleukin-1; D007529:Isoflavones; D047029:Lactams, Macrocyclic; D010750:Phosphoproteins; D011809:Quinones; D014409:Tumor Necrosis Factor-alpha; D017828:Rifabutin; C020754:herbimycin; D019833:Genistein; D011505:Protein-Tyrosine Kinases