In sepsis caused by Gram-negative bacilli, endotoxin is the most critical activator. Lipopolysaccharide (LPS) is the main component of endotoxin, which can combine with various receptors in the body to trigger inflammatory effects. Among them, monocytes and macrophages are the most important effector cells. When endotoxin enters the body, it will change the Toll-like receptor 4 (TLR4) of monocyte-macrophage in the form of the LPS-LBP-CD14 complex. With the participation of transmembrane and nuclear proteins, transcription factors such as NF-KB are finally activated, and a large number of pro-inflammatory and negative inflammatory factors are synthesized and secreted.
Figure 1. Summary of the inhibitory actions of high-dose LBP. (Page M J, et al., 2022)
LBP is a glycoprotein with a molecular weight of 58-60 kd, which is mainly synthesized by the liver and released into the blood. For the first time, researchers isolated and purified lipopolysaccharide-binding protein from rabbit acute reaction serum. LBP exists in normal human and many animal serums, but the general concentration is lower than 0.5 ng/ml. LBP can recognize the lipid A part of LPS, has a high affinity with LPS, can combine with LPS-bearing bacteria or particles, and has the opsonizing effect of promoting the combination of these particles and macrophages. In the process of cell response to LPS, LBP mainly plays a catalytic role. LBP transports LPS monomer from its multimer to CD14, accelerates the combination of LPS and CD14, and one molecule of LBP can promote hundreds of molecules of LPS and CD14 combined. After LPS forms a complex with LBP, it can efficiently bind to soluble CD14 (sCD14) or membrane-bound CD14 (mCD14) receptors and activate cellular responses. Experimental in vitro evidence suggests that the LBP/CD14 system can enhance the sensitivity of various cells to endotoxins, as well as increase the endotoxin's activity hundreds to thousands of times.
LBP not only facilitates the transfer of LPS to the TLR4 complex to maximize LPS-induced signaling but also has multiple functions in lipid transfer and immune regulation in the recognition and control of bacterial infection. The role of LBP in these responses is concentration-dependent. At low concentrations, LBP enhances LPS-induced immune activation, whereas as LBP concentrations rise in the acute phase, LBP inhibits LPS-induced cellular stimulation and promotes LPS clearance to Protect the host from bacterial attack.
Reference
