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From the liver to the blood: How is C-reactive protein produced?
C-reactive protein (CRP) is a circular (ring-shaped) pentameric protein found in plasma, the concentration of which increases in response to inflammation. This acute phase protein originates from the liver and is increased in response to interleukin-6 secretion by macrophages and T cells. The physiological role of CRP is to bind to lysophosphatidylcholine expressed on the surface of dead or damaged cells (and some types of bacteria), thereby activating the complement system via C1q.
CRP is produced by the liver and is influenced by factors released by macrophages, T cells, and adipocytes (fat cells). As a member of the small pentraxin family, CRP plays an important role in the acute inflammatory process and is considered to be the earliest identified pattern recognition receptor (PRR).
The history of CRP began with its discovery by Tillett and Francis in 1930. It was initially thought to be a secretion of a pathogen, but later studies proved that it was a natural protein synthesized by the liver.
Manufacturing process
The synthesis of CRP involves multiple steps. The initial stimulus usually comes from infection, trauma or tumor, which causes macrophages and adipocytes to secrete interleukin-6 (IL-6), thereby prompting the liver to synthesize CRP. Furthermore, this protein exists in serum as a stable pentameric structure, usually in a discoidal morphology.
Function and mechanism of action
CRP mediates activation of the complement system by binding to phosphocholine on the surface of bacterial cells, which promotes the phagocytosis of macrophages and helps to clear necrotic and apoptotic cells and bacteria. Although this mechanism of CRP can promote cell abandonment, it may also lead to the premature death of potentially regenerative ischemic/hypoxic cells.
In addition, CRP is able to bind to Fc-gamma receptor IIa, which is also relevant for the binding of IgG class antibodies. The acute phase response of CRP is due to the increase in cytokines such as IL-6, which promote the synthesis of CRP and fibrinogen in the liver. This process greatly enhances the innate immune defenses, protecting us from a variety of infections.
Serum level measurement
Conventional CRP measurement methods can only detect CRP levels between 10 and 1000 mg/L, while high-sensitivity CRP (hs-CRP) can detect a range of 0.5 to 10 mg/L. hs-CRP is used as a marker for cardiovascular disease risk and is considered high risk when it exceeds 3 mg/L, but low risk when it is below 1 mg/L. In many cases, rapid measurement of CRP is less expensive and more convenient than hs-CRP.
Clinical significance and application
CRP is primarily used as a marker for inflammation. In many pathological conditions, its levels can reflect the progression of the disease or the efficacy of treatment. When inflammation or infection is present, CRP concentrations can rise rapidly to over 500 mg/L, demonstrating its importance in acute inflammation.
However, elevated CRP is not specific to any particular disease, so its use in predicting cardiovascular disease risk still needs to be combined with other parameters, such as cholesterol levels and diabetes.
Future Research on C-Reactive Protein
As scientists gain a deeper understanding of CRP, they are exploring its potential applications in various diseases. Research on CRP and its effects on cardiovascular disease is ongoing, and it has been shown to play a key role in influencing lipid metabolism, atherosclerosis, and various inflammatory responses. The role of CRP may not only be a passive marker, but also an active participant in biological processes.
Therefore, for us, studying the synthesis of CRP and its function in the body will not only help medical diagnosis, but may also guide future treatment strategies. Ultimately, can we fully understand what role CRP plays in disease?
