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Soluble MD-2 is an acute-phase protein and an opsonin for Gram-negative bacteria

Schaeppi, Michela
Elson, Greg
Comte, Rachel
Nobre, Vandack
Published in Blood. 2008, vol. 111, no. 4, p. 2122-31
Abstract Myeloid differentiation factor-2 (MD-2) is a lipopolysaccharide (LPS)-binding protein usually coexpressed with and binding to Toll-like receptor 4 (TLR4), conferring LPS responsiveness of immune cells. MD-2 is also found as a soluble protein. Soluble MD-2 (sMD-2) levels are markedly elevated in plasma from patients with severe infections, and in other fluids from inflamed tissues. We show that sMD-2 is a type II acute-phase protein. Soluble MD-2 mRNA and protein levels are up-regulated in mouse liver after the induction of an acute-phase response. It is secreted by human hepatocytic cells and up-regulated by interleukin-6. Soluble MD-2 binds to Gram-negative but not Gram-positive bacteria, and sMD-2 secreted by hepatocytic cells is an essential cofactor for the activation of TLR4-expressing cells by Gram-negative bacteria. Soluble MD-2 opsonization of Gram-negative bacteria accelerates and enhances phagocytosis, principally by polymorphonuclear neutrophils. In summary, our results demonstrate that sMD-2 is a newly recognized type II acute-phase reactant, an opsonin for Gram-negative bacteria, and a cofactor essential for the activation of TLR4-expressing cells. This suggests that sMD-2 plays a key role in the host innate immune response to Gram-negative infections.
Keywords AnimalsCell LineGram-Negative Bacteria/immunologyHematopoietic Stem Cell TransplantationHumansImmunosuppressionKidneyLymphocyte ActivationLymphocyte Antigen 96/immunologyLymphoma/immunologyMiceMice Inbred BALB CT-Lymphocytes Regulatory/immunologyToll-Like Receptor 4/immunologyTransplantation Isogeneic
PMID: 18056837
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Research group Groupe Pugin Jérôme (Soins intensifs) (587)
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TISSIÈRES, Pierre et al. Soluble MD-2 is an acute-phase protein and an opsonin for Gram-negative bacteria. In: Blood, 2008, vol. 111, n° 4, p. 2122-31. doi: 10.1182/blood-2007-06-097782 https://archive-ouverte.unige.ch/unige:676

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Deposited on : 2009-02-05

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