The body can recognize the presence of LPS (lipopolysaccharide) in time, such as the free LPS in serum or the LPS on the cell membrane of gram-negative bacteria, which is one of the first steps for the body to play its natural immunity. After TLR4, a model recognition receptor in natural immunity recognizes LPS with certain spatial conformation, it can activate relevant signal transduction molecules and induce inflammatory and anti-inflammatory reactions. LBP (lipopolysaccharide-binding protein) has a high affinity with lipid A in LPS, which can identify LPS and LPS on the surface of bacteria in time, and combine with it, showing its biological effects through the following two links.

1. Mediate inflammatory reaction

On the one hand, LBP activates monocytes, macrophages, and neutrophils through mCD14 to produce TNF- α、 IL-1, IL-6, IL-8, and other media, including TNF- α It plays the most important role in the early occurrence of endotoxic shock, and anti-TNF is used at this time- α Monoclonal antibody can improve the survival rate of patients with endotoxic shock. The advanced stage of endotoxemia is positively correlated with the increase of high mobility group protein-1 (HMG-1). At this time, the use of anti-HMG-1 monoclonal antibodies can significantly improve the survival rate of patients with advanced stages of endotoxic shock. LBP can significantly enhance LPS to TNF- α Induce the growth of TNF- α The speed and degree of mRNA transcription promote TNF- α The concentration increased rapidly from 40mg/L to 10000mg/L, while LBP itself could not induce TNF- α mRNA transcription and TNF- α Generation of.

If LBP is subject to dominant-negative mutation so that it does not express LBP, LPS stimulates TNF- α The effect will be significantly reduced. On the other hand, LBP, activated by sCD14, damages vascular endothelial cells, promotes the infiltration of inflammatory mediators to the outside of blood vessels, promotes monocytes, macrophages, neutrophils, and other cells to adhere to vascular endothelial cells, and enters into inflammatory tissues, and aggravates inflammatory reactions; LBP entering the intercellular space can also stimulate macrophages, epithelial cells, and smooth muscle cells, and enhance their response to LPS.

2. Relieve inflammatory reaction

LBP can promote phagocytes such as monocytes, macrophages, and neutrophils to phagocytose-regulated LPS or gram-negative bacteria through conditioning, and timely remove LPS and gram-negative bacteria entering the body; LBP can also catalyze the direct binding of LPS particles and high-density lipoprotein (HDL) particles. The steps are divided into two steps: ① LPS is transferred to sCD14. ② From LPS-sCD14 to HDL. HDL can combine with LPS, make LPS monomer form LPS aggregate, directly neutralize the toxic biological effect of endotoxin, and also promote the internalization activity of LPS. Through internalization into the lysosome for decomposition, LPS loses its toxic effect.

LBP can not only mediate the inflammatory reaction by activating monocytes, macrophages, and other inflammatory mediators to release inflammatory mediators to damage vascular endothelial cells, but also accelerate the host's clearance of LPS and bacteria through conditioning, and catalyze the combination of LPS and HDL to neutralize the biological activity of LPS and reduce the inflammatory reaction, so it can regulate the inflammatory reaction caused by LPS to a certain extent. However, the main physiological function of LBP is to transfer LPS molecules, dissociate LPS aggregates into monomers, and facilitate LPS to expose its internal structure and make it contact with CD14 molecules, that is, to mediate cell reaction. That is to say, the activity of the LBP-mediated activation effect is stronger than that of alleviating inflammatory reaction.

In addition, LPS can also combine with bactericidal permeability-enhancing protein, HDL, lactoferrin, etc. The latter three have the effect of antagonizing endotoxin toxicity. The bactericidal permeability enhancing protein in polymorphonuclear neutrophils can polymerize LPS in a monomer state, and then be swallowed into the lysosome for digestion and decomposition without endotoxin signal, thus antagonizing the toxic effect of endotoxin; In addition, the bactericidal permeability enhancing protein can also mediate the phagocytosis of megakaryocytes. And therefore participate in the host's anti-microbial defense response. Because the affinity of bactericidal osmotic enhancer protein and LPS is 50-70 times that of LBP, its effect of antagonizing LBP is obvious.

To sum up, LBP plays an important role in the occurrence of endotoxemia in the host.