Macrophage Migration Inhibitory Factor Expression In Rat Orthotopic Left Lung Allograft Rejection

Background&AimsMacrophage migration inhibitory factor (MIF),which was found by David in the research of DTH of the skin ,originally described as an inhibitor of the random migration of macrophage, has gotten more attention. Recent study have identified a key role for MIF in a number of inflammatory responses and immune cell-mediated diseases, native or adaptive. cell-mediated immunity was a principal mechanism of organ -graft refection .At present, there are some reports that MIF may play an important role in the cellular immune response mediating acute allograft rejection.The aim of this study was to explore the role of MIF in the pathogenesis of acute lung allograft rejection ,observing MIF expression in the model of orthotopic transplantation of pulmones sinister in rats. Methods32 Rats lung orthotopic transplantation models were established by traditional cuff technique—Pulmonary arterie, vein and bronchi of donors'were anastomosed witn recipients'. Sprague Dawley rats underwent lateral pulmonectomy, and then received an orthotopic Wister lung allograft(Group A ) or an orthotopic SD isograft(group B).And 8 rats as normal control (group C).group A( or group B) of eight animals were killed at day 1 or 5 (as the group A1 or group A2) after transplantation. No immunosuppression was used Staining by H-E.to observing the status of acute rejection by and Immunohistochemical analysis for MIF was performed on the paraffin sections of lung tissues from normal rats and rats underwent allogeneic or isogeneic transplantation.Blood samples were Collecting from heart before resecting the grafts, to determining the serum level of MIF by enzyme-linked immunosorbent assay (ELISA)Results1,Histopathological change of lung graft :the group C was normal control .1st postoperation ,the group A1 and group B1 were both appeared inflammation,with alveoli mild ectasia , focally mixed togethered and alveolar septum focally disrupted or widened,and blood vessel moderately hyperaemia,inflammatory cells infiltrating with packs.The bronchial epithelium focally exuviating.2) 5th day postoperation , there is only a sprinkle of monocytes infiltrating in the graft of group A2 ,the lung tissue's structure is roughly normal ,but the lung graft tissue of group B2 appeared severely monocytes mononuclear macrophages infiltrating sleeve-likely arroud blood vessel or bronchus , complicating endovasculitis .and there will appear cell necrosis , air cavity hemorrhage,and parenchyma necrosis.2,Expression of MIF in rat lung allograft rejection :1) in the normal control group (group C), MIF were mild expressed focally in the tracheal epithelium ,and there were also some weak expression in the bronchic cells and blood vessel endothelium.2)on the 1st day post operation ,in the allogene group (group B1),there were a similar MIF expression between the allogene group (group B1) and the isogene group (group A1) in the extent .MIF was expressed in alveolar epithelium and blood vessel endothelium in a mild extent ,and expressed in the tracheal epithelium moderately ;plymphomonocytes in the mesenchyma expressed MIF in the mild to moderate extent ,compared with group C through analyse of MIF+ cell counting ,have a significant difference between either B1 and C or A1 and C.(P<0.01). 3) on the 5th of postoperation , mononuclear macrophages and lymphocytes in the mesenchyma surrouding vessel sleeve-like ,expressed MIF with severe extent ,compared with other groups, there was a significant difference between group B2 and other groups(group B1,A1,A2,). tracheal epithelium of group C expressed MIF severely.;otherwise that the level of MIF expression in group A2 has significantly decreased(through analyse of MIF(+) cell counting)(P<0.01),compared with group A1,and has no significant diference between group C.(P>0.05)3,The serum levels of MIF :1) in the first day , Compared with those of normal rats ,serum MIF levels of the rats in group A1 and B1 were both increased (p<0.05) , but the levels between group A1 and B1 have no significant difference(P>0.05). 2) In the 5th day , serum MIF levels of the rats in group B2 , Compared with those of rats in group A2 and group A1,B1 ,were significant increased (P<0.01 and P<0.05 , P<0.05). In the 5th day , serum MIF levels of the rats in group A2 , Compared with those of rats in group A1 , were significant decreased (P<0.05), and there is no significant difference(P>0.05),between the serum MIF levels of group A2 and group C.Conclusions1,this study has demonstrated that local MIF production is specifically increased in acute lung allograft rejection in rats.2,The serum MIF levels is specifically increased in acute lung allograft rejection in rats.3,These data suggest a pathological role for MIF in allograft rejection, a postulate which needs to be tested by cytokine blocking studies.