TRANSGENIC MICE EXPRESSING RABBIT C-REACTIVE PROTEIN EXHIBIT DIMINISHED CHEMOTACTIC FACTOR-INDUCED ALVEOLITIS

The acute phase protein, C-reactive protein (CRP), can increase more t han a thousandfold during acute inflammatory states, and it is known t o modulate neutrophil-mediated inflammatory responses. We have previou sly shown that CRP inhibits chemotaxis of C5a-stimulated neutrophils i n vitro and that rabbits with elevated CRP blood levels exhibit dimini shed pulmonary vascular permeability and neutrophil infiltration in a model of alveolitis. To study the effect of CRP on alveolitis induced by different chemoattractants, transgenic mice capable of expressing r abbit CRP in a dietary-inducible fashion were treated with inflammator y doses of the chemoattractants. Intratracheal installation of FMLP (8 x 10(-10) mol), LTB(4) (2 x 10(-11) mol), or IL-8 (5 x 10(-12) mol) i n normal CF1 mice resulted in significant (p < 0.05) influx of neutrop hils and protein into the alveolar space. Transgenic mice with elevate d plasma levels of CRP showed significantly (p < 0.05) diminished infi ltration of neutrophils into bronchoalveolar lavage fluid (BALF) and s ignificant reduction in BALF protein compared with that in normal mice . Rabbit CRP (10 to 500 mu g/ml) inhibited in vitro neutrophil chemota xis in a concentration-dependent fashion when stimulated by the variou s chemoattractants examined. These data show that rabbit CRP can modif y both in vivo and in vitro neutrophil responses to several classes of chemoattractants and that CRP has a significant protective effect in alveolitis by reducing neutrophil influx and protein leakage into the lung.