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Role of MD-2 during sepsis

English title Role of MD-2 during sepsis
Applicant Pugin Jérôme
Number 105770
Funding scheme Project funding (Div. I-III)
Research institution Division des Soins Intensifs de Médecine Département de Médecine Hôpital Cantonal - HUG
Institution of higher education University of Geneva - GE
Main discipline Immunology, Immunopathology
Start/End 01.10.2005 - 30.09.2008
Approved amount 227'000.00
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Keywords (5)

Toll-like receptors; MD-2; sepsis; innate immunity; Bacterial infections

Lay Summary (English)

Lead
Lay summary
MD-2 is a glycoprotein expressed together with Toll-like receptor (TLR)4 at the surface of immune cells, and confers cell responsiveness to bacterial endotoxin (lipopolysaccharide, LPS). In this sense, MD-2 is a central molecule of the innate immunity and is essential for the recognition of Gram-negative bacteria. MD-2 is also found as a soluble protein. The levels of soluble MD-2 in plasma increase in patients with severe sepsis and septic shock. Soluble MD-2 is a critical factor in plasma from patients with sepsis mediating the activation of cells expressing only TLR4 in response to LPS. Soluble MD-2 binds directly to the surface of Gram-negative bacteria. The inhibition of MD-2 using specific monoclonal antibodies abrogated the activation of cells incubated with whole Gram-negative bacteria. We have also shown that soluble MD-2 is a type II acute phase protein, regulated by IL-6, and that a main function of this acute phase reactant is to opsonize Gram-negative bacteria to facilitate phagocytosis by neutrophils. We are currently determining by which mechanism(s) IL-6 and other MD-2 inducers regulate MD-2 expression.
Direct link to Lay Summary Last update: 21.02.2013

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Associated projects

Number Title Start Funding scheme
122034 Role of alarmins and opsonophagocytosis in innate immunity in critically ill patients 01.04.2009 Project funding (Div. I-III)

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