Antimicrobial peptides in lung transplant recipients with bronchiolitis obliterans syndrome

Abstract

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 a-defensins (human neutrophil peptides (HNP) 1-3), and the epithelial cell-derived AMPs human b-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.

Proteomic Bronchiolitis Obliterans Syndrome Risk Monitoring in Lung Transplant Recipients

“…11 was found to be significantly down-regulated in BOS-positive samples. It should be noted that this study confirms the role of CCP and HNPs as BALF markers for BOS suggested by earlier studies (10,11,26,32). CCP is known to be deregulated in a number of diseases that damage the lung epithelium (17,33,34).…”

“…Azurocidin, which has been found to alarm the immune system and exhibit pivotal potential in the pathogenesis of inflammatory conditions (25), was identified in BALF (see Table 3b, Supplemental Digital Content 5, http://links.lww.com/TP/A445). The differential regulation of complement C3 and various proinflammatory peptides further suggests a profound change in the chronic inflammatory reaction supporting the hypothesis that elements of the pulmonary innate immune response play an etiological role in BOS development (26).…”

Circulating cathelicidin LL-37 in adult patients with pulmonary infectious diseases

“…It was also noticed that serum cathelicidin LL-37 levels in children with post-infectious bronchiolitis obliterans were higher as compared with the control group [15]. Likewise, bronchiolitis obliterans syndrome in lung transplant recipients was associated with elevated levels of LL-37 in BAL [16]. Considering the proinflammatory effects of LL-37, it can be assumed that significantly higher levels of LL-37 may exacerbate inflammatory processes during bronchiolitis.…”

Impact of Interleukin-17 on Macrophage Phagocytosis of Apoptotic Neutrophils and Particles

“…Unless this happens, the neutrophils may undergo necrosis or secondary necrosis, phenomena which might lead to severe tissue damage. This type of tissue damage can be observed in severe and sometimes life-threatening conditions, such as chronic lung allograft rejection and acute respiratory distress syndrome [14][15][16][17][18]. With this in mind, we examined whether IL-17 can influence the apoptosis of neutrophils and/or macrophage phagocytosis of apoptotic neutrophils, two critical biological factors that normally control the turnover of neutrophils in mammalian organs.…”