title: In vitro effects of antiphospholipid syndrome-IgG fractions and human monoclonal antiphospholipid IgG antibody on human umbilical vein endothelial cells and monocytes.
abstract: It has been shown that stimulation of endothelial cells and monocytes by antiphospholipid antibodies leads to a prothrombotic state involving upregulation of tissue factor (TF). We examined the in vitro effects of IgG fractions from patients with antiphospholipid syndrome (APS) and of a beta-2-glycoprotein 1-independent human monoclonal antiphospholipid antibody (HL-5B) on human umbilical vein endothelial cells (HUVEC) in comparison to untreated cell controls and to exposure to monoclonal IgG control antibody. We also examined the effect of recombinant monocyte chemoattractant protein-1 (MCP-1) on peripheral blood monocytes. Stimulation of endothelial cells with APS IgG fractions or HL-5B resulted in time-dependent upregulation of MCP-1 mRNA and protein expression. Stimulation with HL-5B also led to time-dependent upregulation of interleukin (IL)-8 and intracellular adhesion molecule-1 (ICAM-1) mRNA and IL-8 protein expressions. Stimulation of monocytes with recombinant MCP-1 resulted in an upregulation of TF mRNA and TF protein. In conclusion these results might represent a mechanism for antiphospholipid antibody-mediated thrombosis in APS patients.
authors.affiliation: Institut für Klinische Chemie und Laboratoriumsmedizin, Universitätsmedizin der Johannes Gutenberg-Universität Mainz, Mainz, Germany.
authors.forename: Natascha
authors.initials: N
authors.lastname: Clemens
authors.forename: Katrin
authors.initials: K
authors.lastname: Frauenknecht
authors.forename: Aviva
authors.initials: A
authors.lastname: Katzav
authors.forename: Clemens
authors.initials: C
authors.lastname: Sommer
authors.forename: Philipp
authors.initials: P
authors.lastname: von Landenberg
mesh_terms: D017152:Antibodies, Antiphospholipid / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D016736:Antiphospholipid Syndrome / Q000276:immunology*; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015151:Immunoblotting; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D017152:Antibodies, Antiphospholipid; D000911:Antibodies, Monoclonal; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D007074:Immunoglobulin G; D016209:Interleukin-8; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D013925:Thromboplastin