Toll-Like Receptor 4 Monoclonal Antibody (Clone HTA125)

The toll-like receptors (TLRs) in mammals comprise a family of transmembrane proteins characterized by multiple copies of leucine rich repeats in the extracellular domain and an interleukin-1 (IL-1) receptor motif in the cytoplasmic domain. Like their counterparts in Drosophila, TLRs signal through adaptor molecules.¹ The TLR family is a phylogenetically conserved mediator of innate immunity that is essential for microbial recognition.² Most mammalian species have between ten and fifteen types of TLRs. Ten functional TLRs (TLR1-10) have been identified in human. Humans also encode a TLR11 gene but it contains several stop codons and protein is not expressed. However, mouse and rat TLR11 are functional, and it is thought that human TLR11 function was lost during evolution. Historically speaking, TLR expression has been most extensively studied in the immune system. Overall, TLRs are highly expressed in immune competent cells, including macrophages, dendritic cells, neutrophils, mucosal epithelial cells and dermal endothelial cells. However, TLRs have also been identified in many other cell types and anatomical tissue locations where they are expressed either constitutively or induced during infection. Among this family of receptors TLR2 and TLR4 have been most studied. These studies have suggested that TLR2 and TLR4 may serve as potential main mediators of LPS signaling.^3,4 The TLR4 cDNA codes for a protein consisting of 799 amino acids with approximate molecular weight of 88 kDa.⁵

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1. Srivastava, M.D., and Srivastava, B.I.S. Expression of mRNA and proteins for toll-like receptors, associated molecules, defensins and LL-37 by SRIK-NKL, a CD8⁺ NK/T cell line. Leuk. Res. 29(7), 813-820 (2005).

2. Gibson, F.C., Hong, C., Chou, H.H., et al. Innate immune recognition of invasive bacteria accelerates atherosclerosis in apolipoprotein E-deficient mice. Circulation 109(22), 2801-2806 (2004).

3. Cognasse, F., Hamzeh, H., Chavarin, P., et al. Evidence of toll-like receptor molecules on human platelets. Immunol. Cell Biol. 83(2), 196-198 (2005).

4. Wong, C.K., Cheung, P.F.Y., Ip, W.K., et al. Intracellular signaling mechanisms regulating toll-like receptor-mediated activation of eosinophils. Am. J. Respir. Cell Mol. Biol. 37, 85-96 (2007).

5. Scheel, O., Papavlassopoulos, M., Blunck, R., et al. Cell activation by ligands of the toll-like receptor and interleukin-1 receptor family depends on the function of the large-conductance potassium channel maxiK in human macrophages. Infect. Immun. 74(7), 4354-4356 (2006).