THE ROLE OF RANTES ON INDUCTION AND PROGRESSION OF EXPERIMENTAL GLOMERULONEPHRI-A STUDY USING RANTES-DEFICIENT MICE

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 12671022
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: CHIBA UNIVERSITY
• Principal Investigator: OGAWA Makoto Chiba University, University Hospital, Assistant, 医学部・附属病院, 助手 (50241956)
• Co-Investigator(Kenkyū-buntansha): UEDA Shiro Graduate School ef Pharmaceutical Sciences, Chiba University, Professor, 大学院・薬学研究院, 教授 (50201348)
• Project Period (FY): 2000 – 2001
• Keywords: CHHEMOKINE / RANTES / GENETICALLY-DEFICIENT MICE / MRL-Fas Ipr mice / ACCELERATED MASUGI NEPHRITIS / AUTOIMMUNE TISSUE INJURY

Research Abstract

The chemokine RANTES is a chemoattractant for monocytes and T cells, and is postulated to participate in many aspects of the immune response. To evaluate the biological roles of RANTES in the induction and developemnet of renal injuries, we generated RANTES-deficient (-/-) mice and examined its susceptibility to the experimental prodedures for production of established animal model of renal injuries. In Masugi glomerulonephritis, histological changes in RANTES-deficient (-/-) mice was almost similat to those in wild mice. We also studied possible role of RANTES in autoimmune tissue injuries by generating RANTES-deficient MRL-Fas Ipr mice. In the RANTES-deficient mice, axillary lymph nodes were significantly reduced in size compared with those of RANTES-intact mice. Flow cytometric analysis revealed that double negative (DN) T cells were significantly reduced. Image analyzer showed that cell-infiltrated areas in peribronchial lesions of the lung were decreased in RANTES-deficient MRL-Fas Ipr mice. Furthermore, we detected continuous expression of RANTES m-RNA in the lung of MRL-Fas Ipr mice. In contrast, the degree of histological renal injuries and survival rate was similar in both genotypes. We speculate that RANTES is involved in the development of peribronchial pulmonary lesions in MRL-Fas Ipr mice. We could not explain the precise mechanism for the difference between the kidney and lung, but it seems quite possible that die role of RANTES in the lung is different from that in the kidney. Further studies using RANTES-deficient mice might contribute to elucidate the mechanism of organ-specific autoimmune tissure injuries.