| LPS from Neisseria meningitidis is crucial for inducing monocyte- and microparticle-associated tissue factor activity but not for tissue factor expression. | |
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MedLine Citation:
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PMID: 22180561 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Reidun Ovstebø; Hans C Dalsbotten Aass; Kari Bente Foss Haug; Anne-Marie Siebke Trøseid; Unni Gopinathan; Peter Kierulf; Jens P Berg; Petter Brandtzaeg; Carola E Henriksson |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-16 |
Journal Detail:
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Title: Innate immunity Volume: - ISSN: 1753-4267 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-19 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101469670 Medline TA: Innate Immun Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Blood Cell Research Unit, Oslo University Hospital, Ullevål, Norway. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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