Anti-Human TLR4/MD-2 (Clone: 7E3)

The monoclonal antibody 10-3521 reacts with the Toll-like receptor 4 (TLR4, CD284)/MD-2 complex. TLRs belong to a family of proteins that specifically recognizes and senses microbial products. They are highly conserved throughout evolution and act as innate immune recognition receptors against many pathogens. TLR4 is a functional receptor for gram-negative bacterial lipopolysaccharides (LPS). TLR4 associates with MD-2 which is absolutely required for LPS-induced activation of TLR4. MD-2 exists as a cell surface protein in association with TLR4. It also exists as secreted forms consisting of MD-2 monomers and multimers (sMD-2). Circulating sMD-2 is mainly present as a doublet of ~20 and 25 kD, representing differentially glycosylated forms. Unlike TLR4, sMD-2 binds directly LPS without the need of soluble CD14 (sCD14). However, LPS-MD-2 interactions are increased when LPS is pretreated with CD14. Only monomeric sMD-2 is biologically active and able to associate with TLR4 and LPS. sMD-2 circulates in plasma of healthy individuals as a non-active, polymeric protein. In septic plasma, the total amount of sMD-2 was strongly elevated and contained both sMD-2 polymers and monomers. Soluble MD-2 is proposed to be an important mediator of organ inflammation during sepsis. During experimental human endotoxemia, the monomeric and total sMD-2 content in plasma increased with the kinetics of an acute phase protein. This parallels enhanced TLR4 costimulatory activity. In vitro studies revealed that sMD-2 release appears to be restricted to endothelial and dendritic cells. The monoclonal antibody 7E3 reacts with the TLR4/MD-2 complex and is able to inhibit the biological activity of the TLR4/MD-2 complex. Protein function: Cooperates with LY96 and CD14 to mediate the innate immune response to bacterial lipopolysaccharide (LPS). Acts via MYD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (PubMed:9237759, PubMed:10835634). Also involved in LPS-independent inflammatory responses triggered by free fatty acids, such as palmitate, and Ni(2+). Responses triggered by Ni(2+) require non-conserved histidines and are, therefore, species-specific (PubMed:20711192). Both M.tuberculosis HSP70 (dnaK) and HSP65 (groEL-2) act via this protein to stimulate NF-kappa-B expression (PubMed:15809303). In complex with TLR6, promotes sterile inflammation in monocytes/macrophages in response to oxidized low-density lipoprotein (oxLDL) or amyloid-beta 42. In this context, the initial signal is provided by oxLDL- or amyloid-beta 42-binding to CD36. This event induces the formation of a heterodimer of TLR4 and TLR6, which is rapidly internalized and triggers inflammatory response, leading to the NF-kappa-B-dependent production of CXCL1, CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling pathway, as well as IL1B secretion. Binds electronegative LDL (LDL(-)) and mediates the cytokine release induced by LDL(-) (PubMed:23880187). Stimulation of monocytes in vitro with M.tuberculosis PstS1 induces p38 MAPK and ERK1/2 activation primarily via TLR2, but also partially via this receptor (PubMed:16622205). [The UniProt Consortium]