Related Experiment Video
Updated: May 26, 2026

Using a Bacterial Pathogen to Probe for Cellular and Organismic-level Host Responses
Published on: February 22, 2019
LPS from Neisseria meningitidis is crucial for inducing monocyte- and microparticle-associated tissue factor activity
Reidun Øvstebø1, Hans C Dalsbotten Aass, Kari Bente Foss Haug
1Blood Cell Research Unit, Section for Research, Department of Medical Biochemistry, Oslo University Hospital, Ullevål, Norway. reidun.ovstebo@medisin.uio.no
Abstract:
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.
Insights
Bacterial lipopolysaccharide (LPS) from Neisseria meningitidis is key for inducing tissue factor (TF)-activity, but not TF-expression. TF-activity requires TF and phosphatidylserine (PS) co-expression on monocytes, which LPS promotes.
Area of Science:
- Microbiology
- Immunology
- Hematology
Background:
- Neisseria meningitidis causes sepsis with coagulopathy.
- Tissue factor (TF) plays a critical role in the coagulation cascade.
- Lipopolysaccharide (LPS) is a major component of Gram-negative bacteria, including N. meningitidis.
Purpose of the Study:
- To evaluate the TF-inducing capacity of N. meningitidis LPS and non-LPS components.
- To investigate the role of LPS presentation (membrane-bound vs. purified) in TF induction.
- To examine the effect of TF modulators and patient plasma on TF activity.
Main Methods:
- Utilized wild-type and LPS-deficient N. meningitidis strains.
- Measured TF-expression and TF-activity on human monocytes and microparticles (MPs) using flow cytometry and clot formation assays.
- Quantified LPS, fibrinopeptide A (FPA), and IL-10 in patient plasmas.
Main Results:
- Purified LPS and wild-type N. meningitidis induced significantly higher TF-activity than LPS-deficient N. meningitidis.
- TF-expression was observed on monocytes with both wild-type and LPS-deficient N. meningitidis.
- Increased TF-activity correlated with coincident TF and phosphatidylserine (PS) exposure on monocytes, a phenomenon induced by LPS.
- Recombinant IL-10 reduced TF-activity, TF/PS co-expression, and microvesiculation.
- Meningococcal septicemia patients showed higher LPS, FPA, and IL-10 levels compared to meningitis patients.
Conclusions:
- N. meningitidis LPS is crucial for inducing TF-activity, not TF-expression.
- TF-activity necessitates co-expression of TF and PS on monocytes, which LPS facilitates.
- IL-10 modulates TF-activity and microvesiculation.
- Elevated LPS, FPA, and IL-10 are markers of meningococcal septicemia.
Related Concept Videos
Formation of Lipopolysaccharides
Bacterial Meningitis II: Pathophysiology

