A New Strategy for Post Lung Transplant Rejection using Chemokine (RANTES)Antibody

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 13671407
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Tokyo Medical University
• Principal Investigator: KANO Takafumi Tokyo Medical University, Medicine Assistant Professor, 医学部, 助手 (70317858)
• Co-Investigator(Kenkyū-buntansha): KATO Harabumi Tokyo Medical University, Medicine, Professor, 医学部, 教授 (20074768) ; HAYASHI Aeru Tokyo Medical University, Medicine, Assistant Professor, 医学部, 助手 (60343513) ; KAJIWARA Naohiro Tokyo Medical University, Medicine, Assistant Professor, 医学部, 助手 (70343514)
• Project Period (FY): 2001 – 2002
• Keywords: Lung transplantation / Rejection / RANTES / Chemokine / Transmigration / Reperfusion injury

Research Abstract

Purpose
Reperfusion injury is considered one of the causes of acute phase injury after transplantation. Pathologically, lung injury is characterized by diffuse injury by inflammatory cells. Analysis of the circulation dynamics ofinflammatory cells is important in terms of investigating rejection, and it has already been reported that as a result of being secreted by respiratory epithelial cells and immune cells, RANTES leads to the clustering of immune cells and plays an important role intransmigration. In this experiment, we suppressed immune cells circulation by controlling the activity ofRANTES, and tried a new approach to the treatment ofrejection after lung transplantation (ischeniia-reperfusion injury).
Methods
We used Lewis rats weighing 250-300 g and created an ischemia-reperfusion model in the left lung. Based on this model, we prepared a group given anti-RANTES antibody before warm ischemia and assessed the effects in terms of histopathology, immunohistochemical staining, and di fferent types of cytokines inBALF.
Results
1. Histopathological findings
Hardly any of the inflammatory cell infiltration or swelling of the vascular endothelium seen in reperfusion injury was observed in the untreated group or the group given anti-RANTES antibody 3 hours before the ischemia.
2. Immunohistochemical findings
LtnmunohistocbemicaJ assessment ofRANTES, JCAM1, ILl-p, and TNF-a as inflammatory reaction markers revealed mild expression in the untreated groupand the group given anti-RANTES antibody 3 hourc before the ischemia, but marked expression was observed in the reperiusion group after warm ischemia.
3. Analysis ofBALF
Measurement of the BALF concentration of each of the components in "2" above by ELISA showed significantly lower concentrations in the group given anti-RANTES antibody 3 hours before the ischemia than in the group reperfused after warm ischemia.
Conclusion
The results of this study suggested the possibility of the ischemia-reperfusion injury after lung transplantation being suppressed by anti-RANTES antibody administration.