title: The Neisseria meningitidis lpxL1 mutant induces less tissue factor expression and activity in primary human monocytes and monocyte-derived microvesicles than the wild type meningococcus.
abstract: Neisseria meningitidis (N. meningitidis) may cause sepsis and meningitis. N. meningitidis with a mutated lpxL1 gene has five, instead of six, acyl chains in the lipid A moiety. Compared with patients infected with the wild type (wt) meningococcus, patients infected with the lpxL1 mutant have a mild meningococcal disease with less systemic inflammation and less coagulopathy. Circulating tissue factor (TF), the main initiator of coagulation, has a central role in the development of coagulation disturbances during sepsis. To study how TF was influenced by the lpxL1 mutant, human primary monocytes and whole blood were incubated with the lpxL1 mutant or the wt meningococcus (H44/76). Monocyte and microvesicle (MV)-associated TF expression and TF-dependent thrombin generation were measured. In both purified monocytes and whole blood, our data show that the lpxL1 mutant is a weaker inducer of monocyte and MV-associated TF compared with the wt. Our data indicate that low levels of circulating TF may contribute to the reduced coagulopathy reported in patients infected with lpxL1 mutants.
authors.affiliation: 1 Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|2 Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
authors.forename: Marit
authors.initials: M
authors.lastname: Hellum
authors.affiliation: 2 Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
authors.forename: Anne-Marie S
authors.initials: AS
authors.lastname: Trøseid
authors.affiliation: 1 Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|2 Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
authors.forename: Jens P
authors.initials: JP
authors.lastname: Berg
authors.affiliation: 1 Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|2 Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
authors.forename: Petter
authors.initials: P
authors.lastname: Brandtzaeg
authors.affiliation: 2 Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
authors.forename: Reidun
authors.initials: R
authors.lastname: Øvstebø
authors.affiliation: 1 Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|2 Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
authors.forename: Carola E
authors.initials: CE
authors.lastname: Henriksson
mesh_terms: D000217:Acyltransferases / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics*; D001777:Blood Coagulation; D055252:Cell-Derived Microparticles / Q000378:metabolism; D002478:Cells, Cultured; D018450:Disease Progression; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000382:microbiology; D008581:Meningitis / Q000276:immunology* / Q000382:microbiology; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology; D009154:Mutation / Q000235:genetics*; D009345:Neisseria meningitidis / Q000235:genetics / Q000276:immunology*; D061251:Primary Cell Culture; D018805:Sepsis / Q000276:immunology* / Q000382:microbiology; D013925:Thromboplastin / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D013925:Thromboplastin; D000217:Acyltransferases; C118473:LpxL protein, bacteria
keywords: Microvesicles; Neisseria meningitidis; lpxL1 mutant; monocytes; sepsis; tissue factor