Complement activation is a defense mechanism of the body, such as killing bacteria through complement. However, when complement is activated, it also causes a series of cascade reactions in the body, forming a variety of complement split products such as C5a, etc. The latter can increase vascular permeability, release a variety of biologically active substances, and attract leukocytes to gather, thereby causing damage of visceral and organ function. Experiments have shown that adding endotoxin (also known as LPS) to sheep red blood cells can passively sensitize red blood cells, produce agglutination, and produce complement-mediated cell lysis in the presence of exogenous endotoxin antibodies. In refractory septic shock, uncontrolled complement activation due to high concentrations of endotoxin can be severely life-threatening. In vitro, experiments have shown that incubation of plasma with LPS can activate the complement cascade to form C3a and terminal complement complexes.
Figure 1. Crosstalk between complement and TLR pathways. (Merle N S, et al., 2015)
Endotoxins can activate the complement cascade reaction, and complement activation forms anaphylatoxins C3a, C5a, and terminal complement complexes. Smooth muscle spasms and contractions can be caused by anaphylatoxins, which can increase vascular permeability and cause cells to release various biologically active substances, including histamine, prostaglandins (PG) and leukotrienes (LT). In addition to promoting leukocyte adhesion and aggregation, it promotes leukocyte adhesion to vascular endothelium, frees them from blood vessels and local concentration, and has a strong chemotactic effect, among which C5a is the strongest. Most studies have found that the intrinsic components of complement C3 and C4 have a protective effect on endotoxic shock, and the terminal complement complex can dissolve and consume target cells, thereby protecting the body. Therefore, endotoxin can activate complement, which is related to the damage and failure of organ function caused by complement activation. At the same time, complement also has the function of sterilizing and protecting against endotoxin shock.
The complement system plays an important role in bacteriolysis and cell lysis, cell adhesion, immune regulation, and inflammatory response. It is a group of proteins that naturally exist in body fluids and cells. In nonspecific immunity, bacterial cell wall LPS can activate C3 through an alternative activation pathway. Studies have found that endotoxin can activate the complement system and cause circulation disorders in the body. Moreover, bacteria or endotoxins can activate complement in various animal models, resulting in anaphylatoxin C3a, C5a, and terminal complement complex, and C5a levels are positively correlated with endotoxin levels. Complement activation is also common in patients with various diseases. To sum up, endotoxin can activate the complement system and trigger a series of changes in tissues and organs.
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