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

Innate Immunity
|December 20, 2011
PubMed

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.