Low-molecular-weight heparins do not modify obliterative airway disease in rat tracheal allografts.
Immunosuppressive and antiproliferative effects of heparin may be beneficial in the field of solid organ transplantation. The aim of this study was to examine the effect of low-molecular-weight heparin (LMWH) compounds on the development of obliterative airway disease (OAD) in the rat tracheal transplant model. Allogenic heterotopic tracheal transplantations were performed from Brown-Norway into Lewis rats. Recipients were treated either with nadroparin, enoxaparin, parnaparin, or vehicle from day 0 until harvesting at day 7 or 21. Graft rejection was morphometrically assessed to determine the extent of luminal obliteration end epithelial necrosis. All tracheal grafts harvested at day 7 demonstrated nearly equivalent degree of luminal obstruction regardless of treatment regimen. Likewise, at day 21 the extent of airway narrowing and the degree of inflammatory cell infiltration were similar among the groups. Moreover, loss of airway epithelium was not prevented by LMWH treatments. Finally, intragraft mRNA expression for transforming growth factor-β1 and platelet-derived growth factor-A, interleukin-2, interferon-γ, and monocyte chemoattractant protein-1 did not differ between the groups. In contrast with findings in other animal models, treatment with LMWH preparations did not modify the development of OAD in rat tracheal allografts.
Fillinger
Janos
J
Department of Pathology, National Koranyi Institute for TB and Pulmonology, Budapest, Hungary.
Antus
Balazs
B
D000818:Animals; D001989:Bronchiolitis Obliterans / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016207:Cytokines / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology / Q000627:therapeutic use*; D006789:Host vs Graft Reaction / Q000187:drug effects*; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D016133:Polymerase Chain Reaction; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D014132:Trachea / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014184:Transplantation, Homologous; D017211:Treatment Failure
D016207:Cytokines; D006495:Heparin, Low-Molecular-Weight; D010982:Platelet-Derived Growth Factor; D053773:Transforming Growth Factor beta1