Structure and Function of Lipopolysaccharide Binding Protein

Abstract

The primary structure of lipopolysaccharide binding protein (LBP), a trace plasma protein that binds to the lipid A moiety of bacterial lipopolysaccharides (LPSs), was deduced by sequencing cloned complementary DNA. LBP shares sequence identity with another LPS binding protein found in granulocytes, bactericidal/permeability-increasing protein, and with cholesterol ester transport protein of the plasma. LBP may control the response to LPS under physiologic conditions by forming high-affinity complexes with LPS that bind to monocytes and macrophages, which then secrete tumor necrosis factor. The identification of this pathway for LPS-induced monocyte stimulation may aid in the development of treatments for diseases in which Gram-negative sepsis or endotoxemia are involved.

Treponemal glycoconjugate inhibits Toll‐like receptor ligand‐induced cell activation by blocking LPS‐binding protein and CD14 functions

“…These results indicate that serum component(s) in the culture medium play a pivotal role in the inhibitory action of Tm-Gp. LBP in serum interacts with and then recruits LPS from the bacterial membrane to another mammalian protein, CD14 [30,31], which is , with or without 50 ? g/ml Tm-Gp in the presence or absence of 50 ng/ml LBP and 500 ng/ml CD14.…”

Characterization of recombinant human HBP/CAP37/azurocidin, a pleiotropic mediator of inflammation‐enhancing LPS‐induced cytokine release from monocytes

“…, an acute-phase protein present in small amounts in serum, is known to be necessary for LPS responses of CD14 receptor-bearing cells, such as neutrophils and monocytes [17][18][19]. LBP lowers the threshold stimulatory concentration of LPS and markedly enhances the LPS-induced cytokine release [20,21].…”

STAT‐1‐mediated repression of monocyte interleukin‐10 gene expression in vivo

“…The gram-negative bacterial cell wall component lipopolysaccharide (LPS) is an endotoxin that triggers a myriad of immunoregulatory cytokines that participate in eliminating the bacterial insult [1]. LPS associates with a 60-kD serum protein called lipidbinding protein and this complex subsequently associates with CD14, a 50-kD glycoprotein surface receptor constitutively expressed primarily by macrophages and monocytes, two cellular components of the innate immune system [2,3]. Once bound to CD14, the LPS/ CD14 complex associates with a separate membranebound receptor Toll-like receptor (TLR)4, a member of a family of specialized pattern recognition receptors called the TLR, so named for their homology to the Drosophila Toll proteins [4,5].…”