Antimicrobial Peptides in Lung Transplant Recipients with Bronchiolitis Obliterans Syndrome

¹ Cardiopulmonary Transplant Unit, Freeman Hospital, Newcastle upon Tyne Applied Immunobiology and Transplantation Research Group, Institute of Cellular Medicine Newcastle University, Newcastle, UK; and Dept of Pulmonology, Leiden University Medical Centre, Leiden, The Netherlands
² Dept of Pulmonology, Leiden University Medical Centre, Leiden, The Netherlands
³ Cardiopulmonary Transplant Unit, Freeman Hospital, Newcastle upon Tyne Applied Immunobiology and Transplantation Research Group, Institute of Cellular Medicine Newcastle University, Newcastle, UK
⁴ Respiratory Research Group, University of Calgary, Alberta, Canada

	Abstract

Mechanisms other than classical alloimmunity are implicated in the pathogenesis of Bronchiolitis Obliterans Syndrome (BOS). We hypothesised that antimicrobial peptides (AMPs), elements of lung innate immune response, have a role in BOS pathogenesis.

We measured pulmonary expression of the neutrophil-derived AMPs hCAP-18/LL-37 and -defensins (HNP1–3), and the epithelial-cell derived AMPs human -defensin-2 (hBD-2), elafin and secretory leukoprotease inhibitor (SLPI) in stable lung transplant recipients and those with BOS, and examined the relationship between airway pathogens and AMP levels.

Bronchoalveolar lavage (BAL) was performed on 46 lung transplant recipients (30 stable, 14 BOS). BAL was cultured for pathogens and ELISAs for AMPs were performed.

Presence of airway pathogens was associated with significantly increased levels of neutrophil-derived and epithelial-derived AMPs. When patients without pathogens in BAL fluid were analysed, recipients with BOS (n=8) had elevated hCAP-18/LL-37 (p=<0.001) and HNP1–3 (p=0.004) compared to stable recipients (n=25). hBD-2 and elafin levels were comparable in BOS and stable recipients, but SLPI levels were reduced (p=<0.001) in BOS.

BOS is associated with elevated airway hCAP18/LL-37 and HNP 1–3 from activated neutrophils, even in the absence of pathogens. Together with reduced airway SLPI this may favour non-alloimmune airway injury with reduced anti-protease defence and increased neutrophil degranulation.

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