Increased bronchoalveolar lavage human β-defensin type 2 in bronchiolitis obliterans syndrome after lung transplantation

Human beta-defensin-2 (HBD)2 is an antimicrobial peptide that participates in the innate host immune defense. HBD2 is present in bronchoalveolar lavage (BAL) fluid during conditions associated with air-way inflammation but not in normal subjects. We measured HBD2 concentrations by semiquantitative Western analysis in BAL of prelung transplant patients (PRE) and postlung-transplant BAL associated with either quiescent histopathology (i.e., without acute cellular rejection or infection) (NORMAL POST) or with bronchiolitis obliterans syndrome (BOS). HBD2 levels were not different for PRE (n=9) versus NORMAL POST-transplant BAL specimens (n=22) (204 +/- 180 vs. 82 +/- 60 pg/mL; P=NS). The BAL HBD2 concentrations were significantly elevated, however, with BOS (n=8) (1,270 430 pg/mL; P<0.001). HBD2 has been previously shown to elicit an adaptive immune response by means of recruitment of immature CD34(+) dendritic cells and memory (CD4(+)/CD45RO(+)) T lymphocytes through interactions with their chemokine receptor, CCR6. Furthermore, HBD2 with CD14 in human tracheobronchial epithelium can complex with toll-like receptors to activate the nuclear factor (NF)-kappaB pathway and therefore promote cytokine gene expression. We therefore speculate that complex interactions between adaptive and innate immunity may contribute to the propagation of airway inflammation in BOS.