LPS-RS (R. sphaeroides) - Cell culture tested - TLR4 Antagonist

LPS from Rhodobacter sphaeroides

Lipopolysaccharide from the photosynthetic bacterium Rhodobacter sphaeroides (LPS-RS) is a potent antagonist of toxic hexa-acylated LPS in human and murine cells [1]. It also prevents LPS-induced shock in mice [1]. Complete competitive inhibition of LPS activity is possible at a 100-fold excess of the antagonist. LPS-RS does not induce TLR4 signaling but is detected by the LAL standard endotoxin detection assay.

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Mode of action

LPS-RS is penta-acylated, and like other under-acylated LPS, appears to use at least two distinct mechanisms to block LPS-dependent activation of Toll-like receptor 4 (TLR4). The primary mechanism consists of direct competition between under-acylated LPS and hexa-acylated LPS for the same binding site on MD-2, while the secondary mechanism involves the ability of under-acylated LPS-MD-2 complexes to inhibit the TLR4 agonist activity of hexa-acylated LPS-MD-2 complexes [2-5].
 

Key features of LPS-RS Standard

• LPS preparation extracted by a phenol-water mixture
• Inhibits TLR4 activity
• Activates TLR2, as it contains other bacterial components, such as lipoproteins
• Detectable using the LAL assay
   

Key features of LPS-RS Ultrapure

• LPS extracted by successive enzymatic hydrolysis steps (phenol-TEA-DOC extraction protocol [6])
• Inhibits TLR4 activity
• Does not activate TLR2, as contaminating lipoproteins have been removed
• Detectable using the LAL assay
  
   

References:

1. Qureshi, N. et al., 1999. Nontoxic RsDPLA as a potent antagonist of toxic lipopolysaccharide. p. 687-98. In: Brade H., Opal S. M., Vogel S. N., and Morrison D. C., eds. Endotoxin in Health and Disease. Marcel Dekker, New York.
2. Coats SR. et al., 2005. MD-2 mediates the ability of tetra-acylated and penta-acylated lipopolysaccharides to antagonize Escherichia coli lipopolysaccharide at the TLR4 signaling complex. J Immunol. 175(7):4490-8.
3. Teghanemt A. et al., 2005. Molecular basis of reduced potency of underacylated endotoxins. J Immunol. 175(7):4669-76.
4. Visintin A. et al., 2005. Pharmacological inhibition of endotoxin responses is achieved by targeting the TLR4 coreceptor, MD-2. J Immunol. 175(10):6465-72.
5. Saitoh S. et al., 2004. Lipid A antagonist, lipid IVa, is distinct from lipid A in interaction with Toll-like receptor 4 (TLR4)-MD-2 and ligand-induced TLR4 oligomerization. Int Immunol. 16(7):961-9.
6. Hirschfeld M. et al., 2000. Cutting edge: repurification of lipopolysaccharide eliminates signaling through both human and murine toll-like receptor 2. J Immunol. 165(2):618-22.