title: Insulinlike growth factor-1 in lung transplants with obliterative bronchiolitis.
abstract: Bronchiolitis obliterans syndrome (BOS) is the major complication limiting survival of lung transplant recipients (Tx patients). The mechanisms underlying this fibrotic process are not known. We assessed IGF-1 and IGFBP-3 expression, critical mediators in different models of pulmonary fibrosis, in nine Tx patients. Three of them developed a BOS at 8, 14, and 17 mo postgraft, respectively. Two of the remaining six displayed a recurrent cytomegalovirus (CMV) infection, and four are in stable condition. IGF-1 mRNA expression was quantitated by RT-PCR in cells from four to six BAL per patient performed during the first 6 mo postgraft. Contrasting with a constantly low expression of IGF-1 mRNA in BAL cells from the six patients without BOS, the three patients with BOS presented marked peaks of IGF-1 on two to five occasions during the study period. These peaks, 3- to 13-fold increased compared with values from the former patients, preceded the diagnosis of BOS by 7, 13, and 17 mo, respectively. On the other hand, IGFBP-3 was highly and exclusively expressed in the three patients with BOS, the mRNA as well as the gene product as demonstrated by Western blotting. Our data strongly argue for a role of IGF-1 and IGFBP-3 in the fibrotic process underlying BOS, and for their possible value as an early marker of this complication.
authors.affiliation: Laboratoire d'Immunologie Pulmonaire and Service de Pneumologie, Hôpital Laënnec, Paris, France.
authors.forename: J M
authors.initials: JM
authors.lastname: Charpin
authors.forename: M
authors.initials: M
authors.lastname: Stern
authors.forename: D
authors.initials: D
authors.lastname: Grenet
authors.forename: D
authors.initials: D
authors.lastname: Israël-Biet
mesh_terms: D001706:Biopsy; D001989:Bronchiolitis Obliterans / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000473:pathology; D016040:Lung Transplantation / Q000473:pathology*; D016133:Polymerase Chain Reaction; D011183:Postoperative Complications / Q000473:pathology*; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I