LBP (lipopolysaccharide-binding protein) has a high affinity with lipid A in LPS (lipopolysaccharide) structure, which can recognize and bind LPS to form the LPS-LBP complex.
On the one hand, the LBP-LPS complex can transmit LPS to the membrane CD14 (mCD14) molecular receptors. After close physical contact between LPS with certain spatial conformation and Toll-like receptor 4 (TLR4) on monocytes, macrophages, neutrophils, and other cells, it can induce TLR4 to undergo receptor dimerization or polymerization to form ligand-receptor complex, activate multiple transcription factors through enzymatic cascade reaction, and promote the expression of cytokines such as TNF-a, IL-1, IL-6 and inflammatory mediators such as chemokine IL-8, It shows the effect of agonist, and can enhance the adhesion between cells, resulting in a series of pathological reactions (inflammatory reactions) and physiological reactions (reactions to kill bacteria and remove endotoxin molecules); If the chemical-spatial conformation of LPS does not have close physical contact with TLR4, it is an antagonistic effect.
On the other hand, for cells without the mCD14 receptor, such as endothelial cells and epithelial cells, it is necessary to activate TLR4 on endothelial cells and epithelial cells through soluble CD14 receptor (sCD14), and sCD14 combines with LPS-LBP to form sCD14-LBP-LPS ternary complex, which can transmit LPS to mCD14 and endothelial cells, It produces a series of biological effects (fever, inflammatory reaction, DIC, etc.) through TLR4. In addition, the body's parenchymal cells, such as hepatocytes, also have mCD14 and TLR4 receptors, which are similar to macrophages. In the absence of CD14 and other receptors, LPS can even directly bind TLR4 to produce effects, but its strength is relatively weak.
LBP combines with endotoxin to form LPS-LBP complex and then combines with mCD14 or sCD14 to stimulate monocytes and vascular endothelial cells, etc., resulting in the activation effect of endotoxin, which brings both beneficial and harmful effects to the body. The above transport is reversible. In this process, LBP acts as a carrier protein to transfer LPS to CD14 and other receptors. In fact, LBP acts as a catalyst to catalyze the combination of LPS and CD14: that is, the N-terminal region of LBP first combines with LPS of LPS aggregate to dissociate it into monomers to form LPS monomer - LBP complex (similar to substrate - enzyme complex), and then combines with CD14 through the C-terminal region of LBP to form LPS-LBP-CD14 complex; After the transfer, LBP separated from the complex and participated in the recycling of its transport function. In other words, LBP catalyzes the combination of LPS and CD14 by acting as a catalyst.