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Inhibition of phagocyte killing of bacteria via inhibitory IGG-FCR signaling

Sepsis is among the leading causes of death in health facilities worldwide. Even with adequate treatment, severe sepsis results in approximately 50% mortality, which indicates that the individual response to the infection is variable. (Moitra, Beal, Belikoff, & Remick, 2012)
In a previous paper published by the Remick laboratory it was determined that the presence of pre-existing, plasma IgG antibodies in mice prior to the onset of sepsis could be responsible for differences in their survival. A Plasma Enhanced Killing (PEK) assay was used to calculate the PEK capacity of plasma i.e. the ability of plasma to augment phagocytic killing of bacteria. PEK was calculated as PEK= (1/log (N)) X 100; where N= number of surviving bacteria; a higher PEK indicated better bacterial killing(Moitra et al., 2012). The prior study also determined that inhibitory IgG probably binds inhibitory Fc receptors on phagocytic cells to result in reduced killing of bacteria.
This published work used the value of the PEK to predict which mice would live and which mice would die when subjected to sepsis from cecal bacteria through the method of cecal ligation and puncture (CLP) to induce sepsis.
The goal of this study was to build on what was already found and go further to demonstrate the pathway of how the blocking of IgG occurs via the Fc𝛄R in bacteria. In prior experiments by the Remick lab it was determined that the plasma from the in vitro plasma enhanced killing assay was related to the survival status of septic mice subjected to cecal ligation and puncture (CLP) model of bacterial peritonitis. The PEK assay relies on the presence of pre-existing antibodies in the plasma augmenting the killing of bacterial cells by polymorphonuclear cells. A high PEK value mean the plasma had the capability to kill bacteria and the mice were more likely to survive compared to those with a lower PEK value who were more likely to die from sepsis.
Two sets of plasma were used, plasma collected with Ethylenediaminetetraacetic acid (EDTA) and plasma collected with heparin as anticoagulants. The data showed the likely presence of inhibitory IgG to be present more in the plasma sample collected with heparin than in those collected with EDTA.

Identiferoai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/36259
Date11 June 2019
CreatorsAmbaah, Ekow
ContributorsRemick, Daniel G.
Source SetsBoston University
Languageen_US
Detected LanguageEnglish
TypeThesis/Dissertation

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