*Purpose: Ischemia reperfusion results in increased transmigration of leukocytes into tissue. This eventually leads to post transplant graft damage after organ transplantation. CD321 (also known as Junctional Adhesion Molecule-A, JAM-A), which is expressed in endothelial tight junctions, and its ligand lymphocyte-function-associated antigen-1 (LFA-1) are demonstrated to be involved in transmigration of leukocyte. This study was designed to investigate the effect of intraportal administration of Anti-CD321 monoclonal antibody (90G4) with regard to liver injury in a murine model of liver warm ischemia reperfusion injury.

*Methods: Warm ischemia of 60 minutes is produced by a micro vessel clip in the 70% of the whole liver in C57BL/6 mouse and followed after reperfusion. 300 μg/mouse of 90G4 or IgG was injected from the portal vein after removing the clip. Serum was collected for liver enzyme and cytokine detection, meanwhile, damaged liver was analyzed by pathology, immunohistochemical staining and flow cytometry.

*Results: The expression of CD321 was internalized in sham group, however, expressed more obvious after liver IRI on the wall of vessels. The levels of GOT and GPT in 90G4 treatment group were significantly decreased compared with IgG group. Moreover, tissue damage observed by histologic study (Suzuki score, cleaved Caspase 3 staining, and TUNEL staining) was consistent with above results. The neutrophil recruitment into the liver were inhibited in 90G4 treatment group after reperfusion. And systemic levels of IL-6 and TNF-α were remarkably reduced in 90G4 group accordingly.

*Conclusions: Intrapotal injection of 90G4 ameliorates ischemia reperfusion injury in a murine model and may provide a potential antibody therapeutics in clinic.

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