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Role of the Lectin Pathway of Complement Activation in Septic and Anaphylactic Shock

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posted on 2013-03-14, 12:30 authored by Michaela Windbichler
The complement system constitutes an important part of innate host defence. Complement activation can be initiated via the classical, lectin or alternative pathway. This work focuses on the role of the lectin pathway in mouse models of septic and anaphylactic shock. As a model of septic shock cecal ligation and puncture (CLP) was used. Complement activation is crucial for survival as mouse strains deficient in C I q and factors Band C2 show a higher mortality than complement-sufficient controls. H2-Bƒ/C2-/- mice also demonstrate an impaired bacterial clearance. The involvement of the lectin pathway can be seen in a rapid and long lasting decrease of serum MBL levels. mRNA expression was not altered during the course of infection. Furthermore, MBL deposition was demonstrated on the abscess that forms after peritoneal infection. Activation of the complement system also occurs during anaphylactic shock. It is believed that the classical pathway is responsible for complement activation, as serum C1q levels decrease during shock. This work shows also an involvement of the lectin pathway with serum MBL levels being diminished after antigen challenge. The mechanism leading to this decrease was investigated. To find out whether complement activation is of pathophysiological consequence in anaphylactic shock, several mouse strains with selective deficiencies in complement components, as well as mast-cell deficient mice were tested. Only mast cell deficient mice were protected from anaphylaxis and showed no decrease in serum MBL levels, indicating that cell derived mediators and not the complement system are crucial for the induction of anaphylaxis. Taken together, these results demonstrate a clear need for the complement system in combating bacterial infections during septic shock. In the case of anaphylaxis, however, complement activation is not causative of the symptoms.

History

Supervisor(s)

Schwaeble, Wilhelm

Date of award

2005-01-01

Awarding institution

University of Leicester

Qualification level

  • Doctoral

Qualification name

  • PhD

Language

en

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