Increased endothelin-1 associated with bacterial infection in lung transplant recipients.
BACKGROUND
Endothelin-1 (ET-1) has fibrogenic and inflammatory properties. Its pathogenic role in pulmonary fibrosis and certain inflammatory airway diseases is now well known. Its production is, in part, triggered by infectious processes. Episodes of infection are suspected to be involved in the development of bronchiolitis obliterans syndrome (BOS), which is the main feature of chronic lung rejection and the major factor limiting the long-term survival of transplanted patients. We postulated that ET-1 is upregulated during infectious complications arising from the graft and that this could partly explain the remodeling of airway structures observed in BOS. We, therefore, set up this study to assess ET-1 expression in relation to complications of the graft in human lung transplant recipients.


METHODS
ET-1 mRNA was quantified by reverse transcription-competitive polymerase chain reaction in cells from 119 samples of bronchoalveolar lavage (BAL) fluid from 17 lung transplant recipients. ET-1 and big ET-1 proteins were assessed in BAL cell culture supernatants by enzyme immunoassay. Transbronchial biopsies (n=21) were stained immunohistochemically for ET-1 receptors.


RESULTS
Episodes of bacterial infection strongly correlated with increased ET-1 mRNA and protein expression. ET-1 receptors were also upregulated during these episodes, especially on endothelial and smooth muscle cells. Five of the seven patients with the highest ET-1 levels subsequently developed BOS.


CONCLUSIONS
These results raise the possibility that ET-1, part of whose production is triggered by infectious postgraft complications, might play a role in the development of BOS through its potential effects on airway remodeling.
Charpin
J M
JM
Laboratoire d'Immunologie Pulmonaire, UPRES EA 220, UFR Biomédicale des Sts Pères, Université Paris V, Paris, France.
Stern
M
M
Lebrun
G
G
Aubin
P
P
Grenet
D
D
Israël-Biet
D
D
D000328:Adult; D001424:Bacterial Infections / Q000209:etiology* / Q000378:metabolism*; D001980:Bronchi / Q000378:metabolism; D001989:Bronchiolitis Obliterans / Q000209:etiology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008171:Lung Diseases / Q000209:etiology* / Q000378:metabolism*; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000378:metabolism; D014018:Tissue Distribution; D015854:Up-Regulation
D019332:Endothelin-1; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin