Reproduction of transfusion-related acute lung injury in an ex vivo lung model.
Leukoagglutinins are implicated in transfusion-related acute lung injury (TRALI). In the present study, severe lung vascular leakage was reproduced by application of a leukoagglutinating antibody of anti-5b specificity in an ex vivo lung model. The antibody originated from a multiparous donor-plasma, observed to cause noncardiogenic edema during transfusion therapy. Heated full plasma (anti-5b-titer 1/128) or purified immunoglobulin G fraction was used for the studies. Ex vivo isolated rabbit lungs were perfused with albumin buffer, and human granulocytes (PMN) were admixed to the recirculating perfusate. In presence of anti-5b antibody plus 5b-positive PMN plus rabbit plasma as complement-source, severe lung edema occurred after a latent period of 3 to 6 hours. Pulmonary artery pressure was only transiently and moderately increased, and the leakage reaction could be traced back to a several-fold increase in lung vascular permeability. In contrast, no vascular leakage was noted in lungs perfused in the absence of anti-5b antibody, PMN, or rabbit plasma. Moreover, no permeability increase occurred on use of 5b-negative PMN. This reproduction of TRALI in an ex vivo lung model corroborates the role of leukoagglutinating antibodies in initiating PMN-dependent respiratory distress and suggests a contribution of concomitant complement activation.
Seeger
W
W
Department of Internal Medicine, Justus-Liebig-University, Giessen, FRG.
Schneider
U
U
Kreusler
B
B
von Witzleben
E
E
Walmrath
D
D
Grimminger
F
F
Neppert
J
J
D000373:Agglutinins / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007962:Leukocytes; D008168:Lung / Q000098:blood supply; D055370:Lung Injury; D008297:Male; D009504:Neutrophils / Q000276:immunology; D010477:Perfusion; D011506:Proteins; D011654:Pulmonary Edema / Q000209:etiology; D011817:Rabbits; D012131:Respiratory Insufficiency / Q000209:etiology; D013577:Syndrome; D065227:Transfusion Reaction
D000373:Agglutinins; D000906:Antibodies; D011506:Proteins; C100155:leukoagglutinins, leukocytes