A new experimental model of in-situ immune complex disease of the lung.
A model of acute immunological lung injury, initiated by the binding of passively administered antibody to an antigen (Concanavalin A (Con A] affixed to the pulmonary endothelium, is described. Pulmonary injury, monitored using the 125I-albumin lung permeability index (LPI) did not occur with antigen deposition alone (LPI 0.235 +/- 0.012). The binding of antibody to the 'planted' lung antigen resulted in injury only when antibody binding exceeded a threshold value of 7.4 +/- 1.4 micrograms antibody globulin per gram of lung. Alevolar-capillary permeability changes were maximal 4 to 8 h after antigen-antibody interaction (LPI at 2 h, 0.353 +/- 0.015: at 4 h, 0.387 +0.33; at 8 h, 0.373 +/- 0.025; at 24 h, 0.289 +/- 0.031; at 48 h, 0.239 +/- 0.022). Lung injury was significantly attenuated by neutrophil (PMN) depletion (LPI at 4 h, 0.325 +/- 0.014: P less than 0.01cf PMN-intact animals), and further reduced by complement depletion (LPI at 4 h, 0.275 +/- 0.023: P less than 0.05 cf PMN-intact and PMN-deplete animals). This model of immune lung injury demonstrates the potential for in situ immune reactions on the pulmonary endothelial surface to induce acute inflammatory injury. Further the model illustrates the cooperative effects of neutrophils and complement in the genesis of inflammation, with both these mediator systems contributing to immunological pulmonary injury.
Boyce
N W
NW
Monash University Department of Medicine, Prince Henry's Hospital, Melbourne, Australia.
Holdsworth
S R
SR
D000208:Acute Disease; D000818:Animals; D003165:Complement System Proteins / Q000172:deficiency; D003208:Concanavalin A / Q000276:immunology; D004195:Disease Models, Animal; D007105:Immune Complex Diseases / Q000209:etiology* / Q000276:immunology; D008168:Lung / Q000276:immunology*; D008171:Lung Diseases / Q000209:etiology* / Q000276:immunology; D008297:Male; D009504:Neutrophils / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains
D003208:Concanavalin A; D003165:Complement System Proteins