INHIBITION OF C5A DOS ARG-INDUCED NEUTROPHIL ALVEOLITIS IN TRANSGENICMICE EXPRESSING C-REACTIVE PROTEIN

C-reactive protein (CRP) is the classic acute phase reactant in man wi th serum levels elevated up to 1,000-fold after the onset of inflammat ion. CRP inhibits chemotaxis of complement (C5a)-stimulated neutrophil s in vitro and rabbits with elevated serum CRP levels exhibit diminish ed neutrophil infiltration and vascular permeability in a model of C5a -induced alveolitis. To specifically evaluate the effect of CRP on C5a -induced neutrophil inflammation in vivo, experiments were performed i n transgenic mice capable of expressing rabbit CRP in an inducible fas hion. After direct instillation of a known inflammatory agent (C5a des Arg) into the airways, transgenic mice with high plasma levels of CRP showed significantly diminished infiltration of neutrophils into bron choalveolar lavage fluid (BALF) and a significant reduction of BALF to tal protein levels compared with normal mice. These data indicate that CRP can diminish lung injury by a reduction in neutrophil influx and protein leakage into alveoli following complement-induced inflammation .