Expression of C-Reactive Protein in the Human Respiratory Tract

Abstract

C-reactive protein (CRP) is a normal constituent of human sera synthesized by hepatocytes and induced by proinflammatory cytokines. The function of this acute-phase reactant includes activation of complement and enhancement of opsonophagocytosis. CRP binds to phosphorylcholine (ChoP), a constituent of eukaryotic membranes that is also found on the cell surface of major bacterial pathogens of the human respiratory tract, including Streptococcus pneumoniae and Haemophilus influenzae. The presence of CRP on mucosal surfaces and role in innate immunity in the human respiratory tract where ChoP-containing organisms reside have not been previously studied. We have shown using a monoclonal antibody to CRP that CRP is present in inflamed (0.17 to 42 g/ml) and uninflamed (<0.05 to 0.88 g/ml) secretions from the human respiratory tract in sufficient quantities for an antimicrobial effect. In addition, the CRP gene was expressed in epithelial cells of the human respiratory tract using in situ hybridization on nasal polyps and reverse transcriptase PCR of pharyngeal cells in culture. The complement-dependent bactericidal activity of normal nasal airway surface fluid and sputum against ChoP-expressing H. influenzae was abolished when the secretions were pretreated to remove CRP. In summary, the results indicate that CRP is present in secretions of the human respiratory tract, that human respiratory epithelial cells are capable of CRP expression, and that this protein may contribute to bacterial clearance in the human respiratory tract.

Inflammatory Cytokines Stimulated C-Reactive Protein Production by Human Coronary Artery Smooth Muscle Cells

“…[5][6][7][8][9] Two studies have shown that both epithelial cells of the respiratory tract and renal epithelium produce CRP. 14,18 Moreover, neuronal cells also Figure 1. Effect of cytokine and LPS treatment on CRP protein production in HCASMCs.…”

C-reactive protein haplotype is associated with high PSA as a marker of metastatic prostate cancer but not with overall cancer risk

“…If we consider early prostate neoplasia progression, where repeated bouts of injury and cell death to the prostate epithelium occur as a result of the action of inflammatory cells in response to pathogens or autoimmune disease (phagocytic cells at inflammatory sites generate reactive oxygen and nitrogen species, which damage cells and the genome) or from direct injury from circulating carcinogens/toxins in the urine, the injury caused to the epithelium triggers a restorative epithelial cell proliferation to replace the damaged cells (Coussens and Werb, 2002;De Marzo et al, 2007 (Haider et al, 2006), and at least epithelial cells of the respiratory tract are capable of CRP expression and secretion (Gould and Weiser, 2001). If local inflammation resolution is dysregulated, the cellular response to the pattern of chronic inflammation changes, such that macrophages and other inflammatory cells generate a great amount of growth factors, cytokines and reactive oxygen species that may cause DNA damage and predispose the patient to neoplasia.…”

The Acute-Phase Reactant C-Reactive Protein Binds to Phosphorylcholine-ExpressingNeisseria meningitidisand Increases Uptake by Human Phagocytes

“…CRP may also play a role in mucosal immunity, since it is present in human nasal secretions and since CRP gene expression has been detected in epithelial cells from nasal polyps and in pharyngeal cell lines (19). Mucosal CRP can bind to PC on the surface of H. influenzae and S. pneumoniae and prevent PC-mediated attachment to epithelial cells via the plateletactivating factor receptor (18).…”