AJP - Lung Cellular and Molecular Physiology, Vol 266, Issue 6 649-L654, Copyright © 1994 by American Physiological Society
Inhibition of C5a des Arg-induced neutrophil alveolitis in transgenic mice expressing C-reactive protein
R. M. Heuertz, D. Xia, D. Samols and R. O. Webster
Department of Internal Medicine, St. Louis University School of Medicine, Missouri 63110-0250.
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.
