title: Histamine reduces GPIbα-mediated adhesion of platelets to TNF-α-activated vascular endothelium.
abstract: Histamine and tumor necrosis factor-α (TNF-α) are critical mediators of acute and chronic inflammation that are generated by mast cells and macrophages in atherosclerotic lesions or systemically during allergic attacks. Both of them induce activation of vascular endothelium and thus may play a role in thrombosis. Here we studied the interplay between histamine and TNF-α in glycoprotein (GP) Ibα-mediated platelet adhesion to cultured human vascular endothelial cells under static and shear flow conditions. The stimulation of endothelial cells with histamine or TNF-α increased the number of adherent or slow rolling GP Ibα-coated microbeads or washed human platelets. However, the application of histamine to endothelium pre-activated by TNF-α inhibited GP Ibα-mediated platelet adhesion. These effects were found to be associated with changes in the concentration of ultra large von Willebrand factor (ULVWF) strings anchored to endothelium. The results of this study indicate that histamine released during mast cell degranulation may cause or inhibit thrombosis, depending on whether it acts on resting endothelial cells or on cells pre-activated by other inflammatory stimuli.
authors.affiliation: Department of Biomedical Engineering, Tulane University, New Orleans, LA 70118, USA.
authors.forename: T P
authors.initials: TP
authors.lastname: Brown
authors.forename: O
authors.initials: O
authors.lastname: Forouzan
authors.forename: S S
authors.initials: SS
authors.lastname: Shevkoplyas
authors.forename: D B
authors.initials: DB
authors.lastname: Khismatullin
mesh_terms: D001792:Blood Platelets / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D006632:Histamine / Q000097:blood* / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D010973:Platelet Adhesiveness / Q000187:drug effects / Q000502:physiology*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood* / Q000494:pharmacology
chemical_list: D019038:Platelet Glycoprotein GPIb-IX Complex; D014409:Tumor Necrosis Factor-alpha; D006632:Histamine