C-reactive protein inhibits increased pulmonary vascular permeability induced by fMLP in isolated rabbit lungs.
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.
Abernathy
V J
VJ
Department of Anesthesiology, St. Louis University School of Medicine, Missouri 63110, USA.
Webster
R O
RO
Dahms
T E
TE
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D000838:Anions / Q000378:metabolism; D002097:C-Reactive Protein / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects*; D066298:In Vitro Techniques; D015289:Leukotrienes / Q000378:metabolism; D008833:Microcirculation / Q000187:drug effects; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D011312:Pressure; D011651:Pulmonary Artery / Q000187:drug effects; D011652:Pulmonary Circulation / Q000187:drug effects; D011817:Rabbits; D013481:Superoxides / Q000378:metabolism; D013929:Thromboxane B2 / Q000378:metabolism
D000838:Anions; D015289:Leukotrienes; D013481:Superoxides; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002097:C-Reactive Protein