C-REACTIVE PROTEIN INHIBITS INCREASED PULMONARY VASCULAR-PERMEABILITYINDUCED BY FMLP IN ISOLATED RABBIT LUNGS

Increased serum concentrations of C-reactive protein (CRP) have previo usly been shown to downregulate neutrophil (PMN) influx and vascular p ermeability changes in models of localized inflammation such as alveol itis [R. M. Heuertz, D. Xia, D. Samols, and R. O. Webster, Am. J. Phys iol. 266 (Lung Cell. Mel. Physiol. 10): L649-L654, 1994]. Experiments in isolated, buffer-perfused rabbit lungs were used to determine wheth er CRP attenuates vascular lung injury induced by PMNs stimulated with the chemotactic peptide N-formylmethionyl-leucyl-phenylalanine (fMLP) . Peritoneal PMN were added to the perfusate of lungs from PMN-deplete d rabbits. Stimulation with fMLP produced an immediate and transient r ise in pulmonary artery pressure that peaked at 35-40 cmH(2)O. An incr ease in permeability occurred 60 min after fMLP, which was marked by a 70% increase (P < 0.05) in filtration coefficient and bronchoalveolar lavage (BAL) protein concentration. CRP pretreatment of PMNs prevente d fMLP-induced increases in permeability and significantly reduced the BAL protein below levels in control lungs (P < 0.05). CRP pretreatmen t of PMNs did not alter the pulmonary arterial presser response to fML P and had no effect on the production of leukotrienes, thromboxane, pr ostacyclin, or superoxide anion induced by fMLP. The mechanism by whic h CRP protects lung tissue from vascular injury induced by activation of PMNs remains unclear.