Natural Killer Cells Recognize Pulmonary Epithelial Stress Molecules during Primary Graft Dysfunction

PurposePrimary graft dysfunction (PGD) occurs in 1/3 of all lung transplants. It is defined by epithelial and innate immune cell infiltration. Natural killer (NK) cells are lymphocytes that activated NKG2D receptor binding specific stress molecules. We hypothesized NK mediate PGD recognizing molecules induced on causing injury via direct cytotoxicity.MethodsIn an established experimental model, left hilar clamp (HC) was compared to sham (S) surgery C57BL/6 mice. Stress (RAE-1, MULT1) receptors were measured flow cytometry median fluorescent intensity (MFI) dissociated cells. Mice given blocking anti-NKG2D or isotype control antibodies preceding HC. Human (MICA, MICB, ULBP1, 3, 2/5/6) bronchial incubated for 4 hours hypoxia (1% O2) versus normoxia conditions. The Mann-Whitney U test applied pairwise comparisons.ResultsNK increased as a percent (p = 0.008) count 0.04) HC (n 5) S lungs infiltrated airways (Figure 1A). following 0.005). MULT1 0.0002) RAE-1 1B, p 0.002) lungs. blockade 9) resulted less pulmonary edema antibody 1C, n 9, 0.04). Hypoxic human 6) had MICB 0.008), ULBP-1 0.05), ULBP-2,5,6 1 D, 0.004) normoxic 6).ConclusionPGD induces ligands leading recruitment contributes PGD. blockade, under investigation clinical trials other diseases, decreased injury. induction during suggests this receptor-ligand interaction may Primary cytotoxicity. In comparisons. 6).