Transgenic mice expressing rabbit C-reactive protein are resistant to endotoxemia

Abstract

C-reactive protein (CRP), the prototypic acute-phase reactant in humans, is synthesized in liver in response to a wide variety of inf lammatory stimuli. We have generated a line of transgenic mice that express rabbit CRP from the rat phosphoenolpyruvate carboxykinase (PEPCK) promoter in response to gluconeogenic signals. Here we show that transgenic mice expressing high levels of CRP were partially protected from a lethal challenge of bacterial lipopolysaccharide compared with littermates in which CRP expression had been suppressed. Similar protection was observed with challenges from platelet-activating factor (PAF) and the combination of tumor necrosis factor ␣ (TNF-␣) plus interleukin 1␤, but not with TNF-␣ alone. We further demonstrate that although PAF was able to bind CRP, the mechanism by which CRP provides protection probably does not involve sequestration of PAF. The biologically inactive precursor of PAF, lyso-PAF, also bound CRP but did not render the transgenic mice sensitive to PAF when CRPexpressing animals were simultaneously challenged with PAF and an excess of lyso-PAF. These results suggest that CRP functions in vivo by modulating host defense systems.

C‐reactive protein impairs human CD14+ monocyte‐derived dendritic cell differentiation, maturation and function

“…CRP may be protective against the development of autoimmunity [12] and anti-inflammation [13] in mice, however human CRP does not protect mice against lipopolysaccharide (LPS) lethality [14]. Additionally, CRP has been shown to be protective against bacterial infections [15], a variety of inflammatory conditions and various mediators of inflammation [16]. Gershov et al demonstrated that CRP may interact with apoptotic cells and promote noninflammatory clearance of apoptotic cells [17].…”

Crystal structures for short-chain pentraxin from zebrafish demonstrate a cyclic trimer with new recognition and effector faces

“…Currently, CRP and SAP are extensively used as biomarkers of various diseases and are targeted in cardiovascular disease treatment (Pepys et al, 2006). These proteins also have potentially broader applications in important diseases, including inflammation, infection and tissue damage (Du Clos, 2003;Ng et al, 2007;Xia and Samols, 1997).…”

C-reactive protein functions as a negative regulator of macrophage activation induced by apoptotic DNA

“…Data are means ± SD of three independent experiments. *** p < 0.001. rabbit CRP transgenic mice (Xia and Samols, 1997). Because of low levels of CRP ( < 5 μg/mL) in mice, the murine model was shown to be useful to test the activity of transgenic or supplemental CRP in vitro and in vivo (Garlanda et al, 2005).…”