C-reactive protein inhibits increased pulmonary microvascular
permeability induced by fmlp in isolated rabbit lungs.
Abernathy, Valerie J., Robert O. Webster, Thomas E. Dahms.
Department of Anesthesiology, Departments of Internal Medicine and
Molecular Microbiology and Immunology, St. Louis University School of
Medicine, St. Louis, Missouri 63110
APStracts 3:0010H, 1996.
Increased serum concentrations of C-reactive protein (CRP) have
previously been shown to down-regulate neutrophil influx and vascular
permeability changes in models of localized inflammation such as
alveolitis (R.M.Heuertz,D.Xia,D.Samols,R.O.Webster Am.J.Physiol.
266:L649-L654, 1994). We conducted experiments using isolated, buffer
perfused, rabbit lungs to determine if CRP attenuates vascular lung
injury induced by neutrophils stimulated with the chemotactic peptide
FMLP (f-met-leu-phe). Rabbits were neutrophil-depleted by treatment
with mechlorethamine 4 days before lung experimentation. After lung
isolation and stabilization, peritoneal neutrophils (5 X 108) from
donor rabbits were stimulated with FMLP (10-6 M) which produced an
immediate and transient rise in pulmonary artery pressure that peaked
at 35-40 cm H2O. An increase in permeability occurred 60 min after
FMLP which was marked by a 70% increase (p < 0.05) in filtration
coefficient (Kf) and bronchial alveolar lavage (BAL) protein
concentrations of 492 + 94.5 [mu]g/ml vs 353.1 + 39.6 [mu]g/ml in
control lungs. CRP pretreatment of neutrophils (4 mg; 10 min; 23
degrees C) prevented increases in permeability following FMLP. In
this group, Kf (baseline) and Kf (60 min FMLP) were 0.0075 + 0.0005
and 0.0074 + 0.0004 gm/min-cm H2O-kg body weight, respectively. BAL
protein concentrations from lungs receiving CRP pretreated
neutrophils followed by FMLP were only 193.8 + 37.9 [mu]g/ml (p
< 0.05). CRP pretreatment of neutrophils did not alter the
pulmonary arterial pressor response to FMLP and had no effect on the
production of leukotrienes, thromboxane, 6-keto PGF1[alpha], or
superoxide anion induced by FMLP. The mechanism by which CRP protects
lung tissue from vascular injury induced by activation of neutrophils
remains unclear.
Received 24 July 1995; accepted in final form 20 December 1995.
APS Manuscript Number H703-5.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 22 January 96