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conferenceseries
.com
Volume 5, Issue 3 (Suppl)
J Infect Dis Ther, an open access journal
ISSN:2332-0877
Infectious Diseases 2017
August 21-23, 2017
3
rd
Annual Congress on
Infectious Diseases
August 21-23, 2017 San Francisco, USA
Roles and mechanisms of DAMPs in sepsis
Guozheng Wang, Simon Abrams
and
Chenghock Tol
University of Liverpool, UK
Statement of the Problem:
The most common pathological change in critical illness is multiple organ failure, which often
leads to death. However, the underlying mechanisms are not fully understood. Recently, the secondary hit by cell breakdown
products causes great attention.
Methodology & Theoretical Orientation:
Both septic animal models and patients with sepsis were investigated. Circulating
histones released after cell death, the most abundant damage-associated molecular pattern (DAMPs), were detected and their
association with organ injury markers was analyzed. Intervention with anti-histone reagents was carried out to confirm the
cause-effect relationship.
Findings:
Circulating histones were dramatically elevated in both animal models and septic patients. Their levels were strongly
associated with the severity of organ injury, particularly lung and cardiac injury. Using anti-histone scFv or non-anticoagulant
heparin could significantly reduce organ injury as well as mortality rates. In addition, histones binding prothrombin initialized
coagulation and significantly contribute to dysregulated coagulation leading to disseminated intravascular coagulation (DIC).
Extracellular histones could interrupt integrity of cell membrane and cause calcium influx to damage cells, stimulate cytokine
release and cause cardiac arrhythmia.
Conclusion & Significance:
DMAPs, particularly histones, play critical roles in sepsis, including inflammation, coagulation
activation, and multiple organ injury. This lays a foundation for future anti-histone intervention to reduce the unacceptably
high mortality rates of sepsis.
Biography
Guozheng Wang is a Reader in University of Liverpool, UK, focuses on critical care medicine, particularly sepsis, using molecular and cellular approach, animal
models and clinical investigation to understand the molecular mechanisms, develop diagnostic and therapeutic tools.
wangg@liv.ac.ukGuozheng Wang et al., J Infect Dis Ther 2017, 5:3 (Suppl)
DOI: 10.4172/2332-0877-C1-026