Complement and endotoxin-induced lung injury in sheep.
Intravenous infusions of endotoxin in sheep cause lung injury characterized by edema due to increased microvascular permeability. Similar increases in pulmonary microvascular permeability are seen in septic patients with the adult respiratory distress syndrome. Since endotoxin-induced lung injury may be mediated by interactions between products of complement activation and polymorphonuclear leukocytes, plasma and lung lymph from six unanesthetized sheep infused with Escherichia coli endotoxin (1.0 micrograms/kg over 30 min) were examined for complement-derived chemotactic activity. By 2-3 hr following infusion of endotoxin, all animals had the increased lung lymph fluid and protein flows characteristic of permeability edema. Preinfusion samples of plasma and lung lymph did not contain chemotactic activity for polymorphonuclear leukocytes. Following infusion of endotoxin, however, significant chemotactic activity was detected in plasma at 0.5-3.5 hr (P less than 0.05) and in lymph at 1.5-6.5 hr (P less than 0.025). The chemotactic activity was heat stable (56 degrees C for 30 min) but was abolished by treatment with antibodies to C5. These data indicate that infusions of endotoxin lead to the generation in plasma, and the appearance in lung lymph, of C5-derived peptides with chemotactic activity for polymorphonuclear leukocytes. C5-derived peptides may account for the pulmonary microvascular leukostasis and endothelial injury that lead to increased permeability edema after infusions of endotoxin.
D000818:Animals; D001769:Blood; D002630:Chemotactic Factors; D002634:Chemotaxis, Leukocyte; D003182:Complement C5 / Q000031:analogs & derivatives / Q000276:immunology*; D015937:Complement C5a, des-Arginine; D004731:Endotoxins / Q000276:immunology*; D004926:Escherichia coli; D005260:Female; D008171:Lung Diseases / Q000276:immunology*; D008196:Lymph / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D011654:Pulmonary Edema / Q000276:immunology; D012756:Sheep; D015054:Zymosan
D002630:Chemotactic Factors; D003182:Complement C5; D015937:Complement C5a, des-Arginine; D004731:Endotoxins; D015054:Zymosan