C-Reactive Protein Increases Oxygen Radical Generation by Neutrophils

Abstract

C-reactive protein (CRP) has been suggested to play a role in the pathogenesis of atherosclerosis. Neutrophil respiratory burst and levels of CRP are increased during infection. The increase in the neutrophil respiratory burst may be due to factors that are elevated in infection, such as cytokines, tumor necrosis factor, platelet-activating factor, and CRP. The direct effect of CRP on the release of oxygen radicals by neutrophils is not known. This investigation was made to determine if CRP affects the generation of oxygen radicals by neutrophils and if this effect is blocked by antioxidants. The effect of various concentrations (1 to 200 microg/mL blood) of CRP on the generation of oxygen radicals by neutrophils was measured as luminol-dependent chemiluminescence (chemiluminescent activity) on a luminometer (Auto Lumat LB953, EG & G Berthold, Gaithersburg, MD). The unit of chemiluminescent activity is the relative light unit and was expressed as relative light unit/white blood cell (RLU/WBC). Chemiluminescent activity of blood without CRP was slightly higher than that of buffer with or without CRP. CRP markedly increased the chemiluminescent activity of blood. There was no significant change in the chemiluminescent activity of WBCs with 1 microg/mL of CRP. The chemiluminescent activity increased significantly with higher concentrations of CRP. The percent increases in the chemiluminescent activity with 2, 5, 10, 25, 50, 100 and 200 microg/mL of CRP were 45%, 72%, 50%, 70%, 52%, 67%, and 68% respectively. Antioxidants (superoxide dismutase, catalase, and dimethylthiourea) blocked CRP-induced oxygen radicals by WBCs. These results suggest that CRP increases the generation of oxygen radicals from the WBCs. CRP-induced atherosclerosis may be mediated through generation of oxygen radicals by neutrophils.

C-reactive protein stimulates superoxide anion release and tissue factor activity in vivo

“…Prasad [32] have shown that in neutrophils, CRP significantly and dose-dependently induces superoxide anion release in vitro, however, no mechanistic studies were undertaken. Exposure of rat mesangial cells to CRP for 60 min led to a dose-dependent increase in superoxide anion release that was nearly threefold greater than that in the control conditions (p < 0.0001) [33].…”

Tamoxifen Alters the Plasma Concentration of Molecules Associated with Cardiovascular Risk in Women with Breast Cancer Undergoing Chemotherapy

“…Furthermore, CRP increases the secretion of monocyte chemoattractant protein-1 [35], which promotes the recruitment of macrophages to the site of arterial injury [36] and contributes to the initiation of atherosclerotic processes [37,38]. CRP has also been shown to increase the levels of oxygen free radicals [39] by inhibiting the production of nitric oxide synthase in vitro [40].…”

Mechanical Strain Induces Expression of C-Reactive Protein in Human Blood Vessels

“…Although a few studies suggested that the proinflammatory effects of commercial CRP in vessels were caused by contamination with lipopolysaccharide, not by CRP itself (Pepys et al, 2005), numerous studies have shown that highly purified CRP (in the absence of lipopolysaccharides and azides) directly activate neutrophils and mononuclear cells, resulting in the production of oxygen free radicals, matrix metalloproteinase, and various cytokines, such as tumor necrosis factor-␣ and IL-1␤ (Prasad, 2004;Verma et al, 2006;Nabata et al, 2008). One study has shown that the minimal amount of lipopolysaccharide derived from commercial CRP does not induce an inflammatory response in vivo (Bisoendial et al, 2005).…”