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C-reactive protein inhibits increased pulmonary vascular permeability induced by fMLP in isolated rabbit lungs
V J Abernathy1, R O Webster, T E Dahms
1Department of Anesthesiology, St. Louis University School of Medicine, Missouri 63110, USA.
Abstract:
Increased serum concentrations of C-reactive protein (CRP) have previously been shown to downregulate neutrophil (PMN) influx and vascular permeability changes in models of localized inflammation such as alveolitis [R. M. Heuertz, D. Xia, D. Samols, and R. O. Webster, Am. J. Physiol. 266 (Lung Cell. Mol. Physiol. 10): L649-L654, 1994]. Experiments in isolated, buffer-perfused rabbit lungs were used to determine whether 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-depleted rabbits. Stimulation with fMLP produced an immediate and transient rise in pulmonary artery pressure that peaked at 35-40 cmH2O. An increase 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 prevented fMLP-induced increases in permeability and significantly reduced the BAL protein below levels in control lungs (P < 0.05). CRP pretreatment of PMNs did not alter the pulmonary arterial pressor response to fMLP and had no effect on the production of leukotrienes, thromboxane, prostacyclin, or superoxide anion induced by fMLP. The mechanism by which CRP protects lung tissue from vascular injury induced by activation of PMNs remains unclear.
Insights
C-reactive protein (CRP) prevents lung injury caused by activated neutrophils (PMNs). CRP pretreatment of PMNs blocked increased vascular permeability and reduced protein leakage in isolated rabbit lungs during inflammation.
Area of Science:
- Pulmonary Medicine
- Inflammation Research
- Biochemistry
Background:
- C-reactive protein (CRP) is known to reduce neutrophil (PMN) influx and vascular permeability in localized inflammation.
- Previous studies demonstrated CRP's anti-inflammatory effects in models like alveolitis.
Purpose of the Study:
- To investigate whether CRP can attenuate vascular lung injury induced by activated neutrophils (PMNs).
- To determine CRP's effect on PMN-induced lung vascular permeability and injury in an ex vivo lung model.
Main Methods:
- Experiments utilized isolated, buffer-perfused rabbit lungs from PMN-depleted rabbits.
- Peritoneal PMNs were added to the perfusate and stimulated with N-formylmethionyl-leucyl-phenylalanine (fMLP).
- Vascular permeability was assessed by measuring filtration coefficient and bronchoalveolar lavage (BAL) protein concentration.
Main Results:
- fMLP stimulation caused a transient rise in pulmonary artery pressure and a significant increase in vascular permeability (70% increase in filtration coefficient and BAL protein).
- CRP pretreatment of PMNs completely prevented the fMLP-induced increases in permeability and BAL protein.
- CRP did not affect the pulmonary pressor response to fMLP or the production of inflammatory mediators like leukotrienes, thromboxane, prostacyclin, or superoxide anion.
Conclusions:
- CRP pretreatment effectively protects lung tissue from vascular injury induced by fMLP-activated PMNs.
- The protective mechanism of CRP against PMN-induced lung injury remains to be elucidated.
- CRP's ability to prevent PMN-mediated vascular leakage highlights its potential role in managing inflammatory lung conditions.