LPS from Neisseria meningitidis is crucial for inducing monocyte- and microparticle-associated tissue factor activity but not for tissue factor expression

• Published in: Innate immunity (London, England) England), 2012-08, Vol.18 (4), p.580-591
• Main Authors: Øvstebø, Reidun, Aass, Hans C Dalsbotten, Haug, Kari Bente Foss, Trøseid, Anne-Marie Siebke, Gopinathan, Unni, Kierulf, Peter, Berg, Jens P, Brandtzaeg, Petter, Henriksson, Carola E
• Format: Article
• Language: English
• Subjects: Blood Coagulation - drug effects; Blood Coagulation - immunology; Cell-Derived Microparticles - drug effects; Cell-Derived Microparticles - immunology; Cells, Cultured; Escherichia coli; Escherichia coli - immunology; Escherichia coli Infections - immunology; Fibrinopeptide A - metabolism; Flow cytometry; Gene Expression Regulation, Bacterial - drug effects; Humans; Interleukin 10; Interleukin-10 - pharmacology; Lipopolysaccharides; Lipopolysaccharides - immunology; Lipoproteins - pharmacology; Meningitis; Meningitis, Meningococcal - blood; Meningitis, Meningococcal - immunology; Meningitis, Meningococcal - microbiology; Meningococcal Infections - blood; Meningococcal Infections - immunology; Meningococcal Infections - microbiology; microparticles; Monocytes; Monocytes - drug effects; Monocytes - immunology; Neisseria meningitidis; Neisseria meningitidis, Serogroup B - immunology; Neisseria meningitidis, Serogroup B - metabolism; phosphatidylserine; Phosphatidylserines - pharmacology; Sepsis; Septicemia; Thromboplastin - genetics; Thromboplastin - metabolism; Tissue factor
• ISSN: 1753-4259; 1753-4267
• DOI: 10.1177/1753425911428230

Neisseria meningitidis causes sepsis with coagulopathy. The present study evaluated the tissue factor (TF)-inducing capacity of bacterial LPS in different presentation forms, i.e. membrane-bound LPS versus purified LPS, and of non-LPS components of N. meningitidis. By using a wild-type N. meningitidis, a mutant N. meningitidis lacking LPS (LPS-deficient N. meningitidis), purified LPS from N. meningitidis and Escherichia coli, we measured TF-expression and TF-activity on human monocytes and microparticles (MPs). The effect of TF-modulators, such as phosphatidylserine (PS), tissue factor pathway inhibitor (TFPI) and recombinant IL-10 (rhIL-10) was investigated. In plasmas from meningococcal patients, fibrinopeptide A (FPA), LPS and IL-10 were quantified. Monocytes and MPs exposed to purified LPS or wild-type N. meningitidis had much higher TF-activity than monocytes and MPs exposed to LPS-deficient N. meningitidis (clot formation assay). Incubation with wild-type N. meningitidis, but also LPS-deficient N. meningitidis, resulted in TF-expression on monocytes (flow cytometry, qRT-PCR). Increased cellular TF-activity is associated with coincident surface-exposure of PS and the number of monocytes positive for both PS and TF was significantly higher for monocytes exposed to wild-type N. meningitidis (7.6%) compared with monocytes exposed to LPS-deficient N. meningitidis (1.8%). Treatment with rhIL-10 reduced monocyte- and MP-associated TF-activity, the number of monocytes positive for both TF and PS, and microvesiculation. Patients with meningococcal septicemia had significantly higher levels of LPS, FPA and IL-10 than patients with distinct meningitis. Our results indicate that LPS from N. meningitidis is crucial for inducing TF-activity, but not for monocyte- and MP-associated TF-expression. TF-activity seems to require coincident expression of TF and PS on monocytes, and LPS induces such double-positive monocytes.