Pseudomonas aeruginosa-induced lung and pleural injury in sheep. Differential protective effect of circulating versus alveolar immunoglobulin G antibody.
The overall objective of these studies was to determine whether IgG antibody to Pseudomonas aeruginosa would modify the acute lung and pleural injury that developed over 24 h after the instillation of 10(10) live P. aeruginosa into the distal airspaces of one lung in unanesthetized sheep. Using a quantitative experimental model to measure protein permeability across the alveolar epithelial, lung endothelial, and pleural mesothelial barriers, the effect of IgG antibody to P. aeruginosa was examined under four different experimental conditions. First, the effect of IgG antibody to P. aeruginosa in the circulation was examined by instilling 10(10) live P. aeruginosa in 5% ovine albumin in sheep that had been vaccinated. Under these conditions, the presence of circulating IgG antibody to P. aeruginosa reduced lung endothelial injury but did not modify the lung epithelial or pleural injury caused by intraalveolar P. aeruginosa. Therefore, the second experimental protocol determined the effect of instilling immune serum from a sheep that had been vaccinated so that IgG antibody to P. aeruginosa was present in both the circulation and in the airspaces along with instillation of live bacteria. Under these conditions, injury to the lung endothelium, alveolar epithelium, and pleural space was completely prevented. Therefore, the third protocol examined the protective effect of instillation of IgG antibody to P. aeruginosa in the airspaces concurrent with the live bacteria. Interestingly, intraalveolar IgG antibody to P. aeruginosa prevented all evidence of lung epithelial and pleural injury, and this effect was associated with a marked decrease in the number of viable bacteria in the lung after 24 h. Therefore, the fourth protocol examined the prophylactic effect of instillation of the specific IgG antibody to P. aeruginosa 24 h before instillation of the bacteria. With this prophylactic regimen, epithelial, endothelial, and pleural injury were prevented, and there was a significant decrease in the number of bacteria recovered from the lung. Thus, delivery of IgG antibody to P. aeruginosa the distal airspaces of the lung alone may provide a novel therapeutic approach to preventing acute pulmonary infection caused by P. aeruginosa.
Cardiovascular Research Institute, University of California, San Francisco 94143.
J F
JF
Pittet
M A
MA
Matthay
G
G
Pier
M
M
Grady
J P
JP
Wiener-Kronish
D000818:Animals; D000907:Antibodies, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology; D001428:Bacterial Vaccines / Q000276:immunology; D004727:Endothelium / Q000502:physiology; D004848:Epithelium / Q000502:physiology; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D008171:Lung Diseases / Q000276:immunology* / Q000382:microbiology; D010539:Permeability; D010998:Pleurisy / Q000382:microbiology*; D011506:Proteins / Q000378:metabolism; D011552:Pseudomonas Infections / Q000276:immunology* / Q000517:prevention & control; D011550:Pseudomonas aeruginosa / Q000276:immunology / Q000472:pathogenicity*; D011650:Pulmonary Alveoli / Q000276:immunology; D012756:Sheep
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D007074:Immunoglobulin G; D011506:Proteins