Trial Lecture - time and place
See Trial Lecture.
Adjudication committee
- 1st opponent: Professor Egil Lien, Umass Medical School
- 2nd opponent: Adjunct Professor Ole Lars Brekke, University of Tromsø
- Committee Chair: Associate Professor Anne-Marthe Bakken Kran, University of Oslo
Chair of the Defence
Professor Emeritus Lars Mørkrid
Principal Supervisor
Associate Professor Carola Elisabeth Henriksson
Summary
The meningococcus, Neisseria meningitidis (Nm) can cause meningitis or severe sepsis. The thesis contributes to expand the knowledge about how a white blood cell, the monocyte, contributes to a massive inflammation and coagulation response in sepsis caused by Nm. After the addition of the wild type Nm to monocyte cultures or whole blood, Aass et al. have shown that the responses of the monocyte are: 1) to release cytokines 2) to increase the expression of the coagulation protein tissue factor (TF) on the surface and 3) to release TF-exposing small vesicles (microvesicles, MVs) from the cell surface. Those processes are initiated when the monocyte recognizes lipopolysaccharides (LPS) in the bacterial membrane. Aass et al. have shown that Nm without LPS, or with a mutated LPS with a changed structure, has a reduced ability to: 1) produce cytokines, 2) induce expression of TF on the monocyte surface and 3) release procoagulant MVs. Aass et al. have also shown that the presence of the anti-inflammatory protein interleukin-10 dampens the production of cytokines, TF and procoagulant MVs. MVs are very small (< 1 µM), and may be procoagulant if they carry TF. Therefore, TF bearing MVs might be circulating biomarkers of thrombotic events, and flow cytometry is a method to measure them. However, due to their small size, measurement of TF on MVs by flow cytometry is very challenging. Aass et al. have measured the number of MVs by flow cytometry and found that the antibody solution, used to visualize the proteins on the surface of the MVs, could contain aggregates of antibodies. These aggregating antibodies were able to interfere in the measurements and mimic the presence of “true” MVs. Aass et al. have shown that the aggregates in the antibody solution could be removed by centrifugation of the antibody solution before use, and this is now a procedure that is recommended by the MV research community.
Additional information
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