HLA class II antibodies induce TRALI in an ex vivo rat lung model in the presence of human neutrophils and matched human monocytes. (A) In the presence of neutrophils, HLA class II antibodies and monocytes that do not bear cognate antigen(s), a minor increase in the capillary filtration coefficient (Kfc) and lung weight is observed (○), but this increase is not different from results obtained with control plasma (●). In contrast, the presence of the same antibodies, neutrophils, but matched monocytes, leads to a significant increase in Kfc and lung weight after 35 minutes and severe edema after 70 minutes (■; P < .01). (B) The effect obtained with plasma, matched monocytes, and neutrophils can be abolished if human monocytes (▵) or human monocytes (▴) are not added to the circulation; n = 3 for each experiment. Results are given as mean values ± SD. (C) Clustering of leukocytes (red) in pulmonary capillaries after the addition of monocyte supernatant or plasma containing HLA class II antibodies to the perfusion circuit (hematoxylin and eosin and antimyeloperoxidase staining). If rat lungs were perfused with human neutrophils and supernatant from monocyte cultures incubated with plasma containing either unmatched (i) or matched (ii) HLA class II antibodies, leukocyte clustering is only observed after the addition of matched supernatant (ii). If rat lungs were perfused with human neutrophils, monocytes, and human plasma containing HLA class II antibodies that either were unmatched (iii) or matched (iv) to the circulating monocytes, clustering of leukocytes is only observed in the presence of matched HLA class II antibodies (iv).
