Inhibition of C5a des Arg-induced neutrophil alveolitis in transgenic mice expressing C-reactive protein.
C-reactive protein (CRP) is the classic acute phase reactant in man with serum levels elevated up to 1,000-fold after the onset of inflammation. CRP inhibits chemotaxis of complement (C5a)-stimulated neutrophils in vitro and rabbits with elevated serum CRP levels exhibit diminished 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 in transgenic mice capable of expressing rabbit CRP in an inducible fashion. 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 bronchoalveolar lavage fluid (BALF) and a significant reduction of BALF total 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.
Department of Internal Medicine, St. Louis University School of Medicine, Missouri 63110-0250.
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Heuertz
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Xia
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Samols
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Webster
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte; D015937:Complement C5a, des-Arginine; D004032:Diet; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D009504:Neutrophils / Q000502:physiology*; D011014:Pneumonia / Q000378:metabolism* / Q000517:prevention & control*; D011650:Pulmonary Alveoli; D011817:Rabbits; D051381:Rats
D015937:Complement C5a, des-Arginine; D002097:C-Reactive Protein