

Other version: http://bloodjournal.hematologylibrary.org/cgi/content/full/111/4/2122
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Soluble MD-2 is an acute-phase protein and an opsonin for Gram-negative bacteria |
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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 | Animals — Cell Line — Gram-Negative Bacteria/immunology — Hematopoietic Stem Cell Transplantation — Humans — Immunosuppression — Kidney — Lymphocyte Activation — Lymphocyte Antigen 96/immunology — Lymphoma/immunology — Mice — Mice Inbred BALB C — T-Lymphocytes Regulatory/immunology — Toll-Like Receptor 4/immunology — Transplantation Isogeneic | |
Identifiers | PMID: 18056837 | |
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![]() ![]() Other version: http://bloodjournal.hematologylibrary.org/cgi/content/full/111/4/2122 |
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Structures |
Faculté de médecine / Section de médecine clinique / Département d'anesthésiologie, pharmacologie, soins intensifs et urgences |
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Research group | Groupe Pugin Jérôme (Soins intensifs) (587) | |
Citation (ISO format) | 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 |