ReviewC-reactive protein and lung diseases
Introduction
C-reactive protein (CRP), a prototypical acute-phase protein in humans and other animal species, is one of the most frequently used markers of inflammation. CRP is known to be synthesized by liver cells in response to pro-inflammatory cytokines (Marnell et al., 2005). CRP concentrations in blood are typically extremely low in healthy individuals, but may be fast increased after induction of inflammatory response associated with infections, autoimmune and cardiovascular diseases, as well as sepsis and cancer. Raised CRP level can also be a predictor of cardiovascular diseases and is used as a marker of systemic inflammation in various conditions. For instance, after sepsis, acute myocardial infarction or tissue damage, serum levels of CRP elevated in some cases up to 1000-fold within 1–2 days in correlation with the magnitude of tissue injury or the severity of inflammation.
CRP binds to normal cells, including platelets, phagocytes, and others, as well as to dead or damaged cells. When CRP is bound to pathogens or dying/dead cells, it is recognized by a complement component C1q and activates the classical complement pathway or may also stimulate responses from phagocytic cells via the binding to Fcγ receptors (Marnell et al., 2005, Mold et al., 2002a). Thus, CRP can identify a number of pathogens and altered cells and, therefore, induce their removal by the humoral arm of innate immunity. However, the great number of records indicate that CRP has both the destructive, as well as protective effects (Griselli et al., 1999, Torzewski et al., 2000, Zwaka et al., 2001). CRP that may serve as a predictor of cardiovascular risk is involved in the pathogenesis of arteriosclerotic lesions and can increase tissue damage in acute myocardial infarction and other inflammatory diseases (Berton et al., 2003).
Recent observations suggest that a high level of CRP could be involved in the pathogenesis of cancer. For instance, CRP is a systemic biomarker of reduced lung function and a predictive marker in cystic fibrosis and chronic obstructive pulmonary disease that can also serve as a systemic biomarker of lung inflammation. CRP which is produced locally in the lungs in addition to being released by the liver cells is very important as well. However, its exact function in the lungs and the pathways mediating its involvement in different lung pathologies are not revealed.
New mechanistic, systematic and clinical studies are needed to understand the role of CRP in lung function and lung diseases. These findings could have broad implications. If an unusual role of CRP in the pulmonary tissue is confirmed, some of the conventional knowledge regarding the role of CRP in human diseases may require reappraisal.
Section snippets
CRP structure
CRP (PDBs: 1BO9; 1CRV; 1GNH; 1LJ7; 3L2Y; 3PVN) is a protein with an annular pentameric disk shape belonging to the pentraxin protein family. It consists of the cyclical arrangement of five identical non-covalently bound subunits (protomers) set symmetrically around a central pore (Fig. 1) (Gupta et al., 2012, Shrive et al., 1996, Thompson et al., 1999). Each subunit is oriented into two antiparallel β-sheets and binds two Ca++ ions, which participate in the binding of some of its ligands to
Local CRP production in the lung
New studies have recently revealed that LPS induces CRP production in the lung epithelial cell line A549, whereas Atorvastatin (LIPITOR®), an antihyperlipidemic agent that acts by inhibiting cholesterol synthesis, down-regulates LPS-induced CRP expression. These data have demonstrated that statins, including Atorvastatin, ameliorate lung inflammation by regulating CRP production in human lung epithelial cells (Xing et al., 2011). Other studies have revealed an increase in CRP expression and
Protective CRP function in the lungs (acute inflammation)
Deregulated inflammatory processes usually lead to a variety of diseases. Acute lung injury is one of known conditions where incapability to regulate inflammatory response in the lungs causes self-induced tissue injury and loss of organ function. The magnitude of the acute phase response is related to the severity of the inflammation or the extent of tissue injury (Heuertz and Webster, 1997).
Conclusion remarks
In spite of the accumulation of clinical data about potential effects of CRP protein on human physiology, it is important to realize that the function of this remarkable protein remains unclear. A putative role for CRP has frequently been hypothesized; however the functional data to determine potential casual CRP pathways are still needed. Many experimental studies are required to finally clarify how CRP participates in pathophysiology of different lung diseases. It is likely that CRP induction
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