Tissières P Dunn-Siegrist I Schäppi M Elson G Comte R Nobre V Pugin J 2008 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. https://sonar.ch/global/documents/182560 eng info:eu-repo/semantics/altIdentifier/doi/10.1182/blood-2007-06-097782 info:eu-repo/semantics/altIdentifier/pmid/18056837 Blood. - 2008 Animals Cell Line Gram-Negative Bacteria Hematopoietic Stem Cell Transplantation Humans Immunosuppression Kidney Lymphocyte Activation Lymphocyte Antigen 96 Lymphoma Mice Mice, Inbred BALB C T-Lymphocytes, Regulatory Toll-Like Receptor 4 Transplantation, Isogeneic Soluble MD-2 is an acute-phase protein and an opsonin for Gram-negative bacteria. http://purl.org/coar/resource_type/c_6501