Lung inflammation induced by complement-derived chemotactic fragments in the alveolus.
The intratracheal injection into rabbits of low molecular weight C5-derived chemotactic fragments (C5fr), prepared from zymosan-activated serum, induced an acute pulmonary inflammation characterized by intraalveolar accumulation of neutrophils, erythrocytes, and edema fluid. In separate experiments, depletion of circulating pulmonary neutrophils and absorption of C5fr with immobilized antibody to homogenous human C5a prevented the observed inflammatory changes, indicating a requirement for these two elements in initiating this reaction. When examined by transmission and scanning electron microscopy, lungs of C5fr-injected rabbits revealed pulmonary neutrophils, often appearing partially degranulated, in alveolar, pulmonary capillary, and interstitial spaces. Alveolar spaces and, less often, the interstitial compartment contained fibrinoid deposits with leukocytes and erythrocytes enmeshed in the fibrin strands. Injury to the pulmonary vascular endothelium consisted of bleb formation in capillaries and endothelial basement membrane separation with subendothelial accumulation of inflammatory cells in venules. Type I, but not type II, epithelial cell damage included blebbing and epithelial cell basement membrane detachment. Endothelial and epithelial layer damage was always associated with pulmonary neutrophils continguous to the injured structures. These studies indicate the potential for alveolar epithelial and capillary injury in neutrophil-associated pulmonary inflammation resulting from intraalveolar accumulation of chemotactic substances.
D000818:Animals; D002634:Chemotaxis, Leukocyte; D003182:Complement C5 / Q000378:metabolism*; D004487:Edema; D005260:Female; D005337:Fibrin / Q000378:metabolism; D006470:Hemorrhage; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D008168:Lung / Q000648:ultrastructure; D008171:Lung Diseases / Q000276:immunology* / Q000473:pathology; D008297:Male; D008855:Microscopy, Electron, Scanning; D009504:Neutrophils / Q000502:physiology*; D011817:Rabbits
D003182:Complement C5; D005337:Fibrin