Antimicrobial peptides in lung transplant recipients with bronchiolitis obliterans syndrome.
Mechanisms other than classical alloimmunity are implicated in the pathogenesis of bronchiolitis obliterans syndrome (BOS). It was hypothesised that antimicrobial peptides (AMPs), elements of the innate immune response, have a role in BOS pathogenesis. Pulmonary expression of the neutrophil-derived AMPs human cathelicidin (hCAP)-18/LL-37 and alpha-defensins (human neutrophil peptides (HNP) 1-3), and the epithelial cell-derived AMPs human beta-defensin (hBD)-2, elafin and secretory leukoprotease inhibitor (SLPI) were measured in stable lung transplant recipients and those with BOS. The relationship between airway pathogens and AMP levels was examined. Bronchoalveolar lavage (BAL) was performed on 44 lung transplant recipients (30 stable, 14 with BOS). BAL was cultured for pathogens and ELISA for AMPs was performed. The 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, eight recipients with BOS had elevated hCAP-18/LL-37 and HNP 1-3 compared with 25 stable recipients. hBD-2 and elafin levels were comparable in BOS and stable recipients, but SLPI levels were reduced in BOS. Bronchiolitis obliterans syndrome is associated with elevated airway human cathelicidin 18/LL-37 and human neutrophil peptides 1-3 from activated neutrophils, even in the absence of pathogens. Together with reduced airway secretory leukoprotease inhibitor this may favour nonalloimmune airway injury with reduced antiprotease defence and increased neutrophil degranulation.
Cardiopulmonary Transplant Unit, Freeman Hospital, Institute of Cellular Medicine Newcastle University, Newcastle upon Tyne, UK. R.Anderson@lumc.nl
R L
RL
Anderson
P S
PS
Hiemstra
C
C
Ward
I A
IA
Forrest
D
D
Murphy
D
D
Proud
J
J
Lordan
P A
PA
Corris
A J
AJ
Fisher
D000328:Adult; D023181:Antimicrobial Cationic Peptides; D001989:Bronchiolitis Obliterans / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D016040:Lung Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology; D053481:Secretory Leukocyte Peptidase Inhibitor; D023084:alpha-Defensins; D054804:Cathelicidins
D023181:Antimicrobial Cationic Peptides; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; D023084:alpha-Defensins; C406413:human neutrophil peptide 1; C406416:human neutrophil peptide 2; C406427:human neutrophil peptide 3; D054804:Cathelicidins