title: Material-induced tissue factor expression but not CD11b upregulation depends on the presence of platelets.
abstract: Biomaterials activate leukocytes as well as platelets when exposed to blood. One feature of leukocyte activation at least at times beyond a few hours is tissue factor expression, contributing to a procoagulant state. We show here that platelet activation and specifically platelet-monocyte aggregate formation appears to be a precondition for tissue factor expression. Material-induced Tissue Factor (TF) expression by isolated leukocytes (6 x 10(6) cells/mL) resuspended in increasing concentrations of platelets in plasma was elevated when the platelet concentration was 50 x 10(6) platelets/mL or more; at lower platelet concentrations (1-25 x 10(6). cells/mL) the TF expression remained at background levels. On the other hand, significant CD11b upregulation was observed on leukocytes, in bulk and adherent to beads, at all platelet concentrations. This platelet effect on material-induced TF expression appeared to be mediated by the formation of platelet-monocyte aggregates. Anti-P-selectin, which blocked the association between platelets and leukocytes, reduced monocyte adhesion and material-induced TF expression for bulk monocytes. Anti-GPIIb/IIIa, a GPIIb/IIIa platelet antagonist, also reduced monocyte adhesion and material-induced TF expression in the bulk, most likely due to its inhibiting effect on the formation of platelet-monocyte aggregates, secondary to platelet activation. However, the antibody-associated reductions for bulk leukocytes (mainly neutrophils) were small and incomplete. Similar levels of TF expression, in the bulk, were observed with both polystyrene (PS), a strong platelet activator, and polyethylene glycol-modified PEG (PS-PEG), a mild platelet activator. The role of platelets in material-induced TF expression appears to be mediated in part via the formation of platelet-monocyte aggregates, although other mechanisms are likely also involved.
authors: Department of Chemical Engineering and Applied Chemistry, Institute of Biomaterials and Biomedical Engineering, University of Toronto, 4 Taddle Creek Road, Room 407D, Toronto, Canada M5S 3G9.
authors: M B
authors: MB
authors: Gorbet
authors: M V
authors: MV
authors: Sefton
mesh_terms: D001672:Biocompatible Materials / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D039481:CD11b Antigen / Q000096:biosynthesis*; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D008863:Microspheres; D015539:Platelet Activation / Q000187:drug effects; D020959:Polyethylene / Q000494:pharmacology; D013925:Thromboplastin / Q000096:biosynthesis*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D001672:Biocompatible Materials; D039481:CD11b Antigen; D020959:Polyethylene; D013925:Thromboplastin