Increased Bronchoalveolar Lavage Human β-Defensin Type 2 in Bronchiolitis Obliterans Syndrome after Lung Transplantation

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Abstract
Human β-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 airway 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+ 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)-κB 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.

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