TY - JOUR T1 - Development of a novel model of obliterative bronchiolitis following orthotopic lung transplantation in the rat JF - European Respiratory Journal JO - Eur Respir J VL - 38 IS - Suppl 55 SP - 224 AU - Marta Vadori AU - Francesca Lunardi AU - Dedja Arben AU - Antonio De Filippis AU - Emanuele Cozzi AU - Federico Rea AU - Fiorella Calabrese Y1 - 2011/09/01 UR - http://erj.ersjournals.com/content/38/Suppl_55/224.abstract N2 - Background. Transplantation (Tx) is the only effective treatment for several end-stage lung diseases, but long-term survival after Tx is precluded by the development of obliterative bronchiolitis (OB). The specific etiology and pathogenesis of OB are not fully understood. Animal models could be crucial to elucidate the immunological and non-immunological pathogenetic mechanisms leading to OB, to identify early markers and to test effectiveness of new treatments.Methods: Left lung allografts from Lewis rats were orthotopically transplanted into Fisher 344 rats [n=19]. Animals were sacrificed at day 30 [group A, n=6] or day 90 [group B, n=6; C, n=4; D, n=3] post-transplantation. In animals from group C and D, cyclosporine A (CyA) was administered from day 1 to 7 or from day 7 to 14, respectively. Following HE-staining, lung rejection was graded according to the working formulation of ISHLT. The presence of circulating donor-specific (DSA) antibodies was determined by flow cytometry.Results: Acute rejection (AR) occurred in 25 to 33% of the animals in the different groups. OB occurred in 17% of animals in group A, in 33% of animals in group B and D, and in 75% of animals in group C. High levels of DSA IgG were observed in all cases of AR and, to a lower extent, in all animals with OB. Furthermore, early administration of CyA reduced the levels of DSA but did not prevent OB occurrence.Conclusions: A novel model of pulmonary OB was developed in the rat. To obtain a reproducible onset of OB, short-term and sub therapeutic CyA administration appears indispensable, at least in our species combination. Furthermore, a 90-day postoperative period is required for OB to take place. ER -