[Frontiers in Bioscience 14, 1807-1814, January 1, 2009]

The role of chemokines in acute renal allograft rejection and chronic allograft injury

Michael Fischereder1, Bernd Schroppel2

1Medizinische Poliklinik - Campus Innenstadt, Klinikum der Ludwig-Maximilians Universitaet Pettenkoferstr. 8a 80336 Munich, Germany, 2Division of Nephrology, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1243, New York, NY 10029, U.S.A.

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Characterization of the role of chemokines in allograft dysfunction using animal models
3.1. Pharmacological anti-chemokine strategies
4. Chemokine biology in acute and chronic human transplant rejection
4.1. Antigen-independent injury
4.2. Antigen-dependent injury
4.2.1. Acute transplant rejection
4.2.2. Chronic transplant rejection
5. Effect of genetic variability in the chemokine system in clinical transplantation
6. Pharmacological anti-chemokine strategies in non-human primate and clinical kidney transplantation
6.1. Non-human primate
6.2. Clinical data
6.3. Potential side effects of chemokine antagonism
7. Conclusion
8. Acknowledgements
9. References

1. ABSTRACT

Short and long term outcome of renal transplantation are determined by acute and chronic rejection processes. In acute transplant rejection, expression of chemokines occurs in different renal compartments where it is triggered through various stimuli e.g. brain death, ischemia, reperfusion, and HLA-mismatch. The induction of chemokine expression precedes the process of organ recovery and extends well into the late course of clinical allograft injury. Chemokines function mainly as chemoattractants for leukocytes, monocytes, neutrophils, and other effector cells from the blood to sites of infection or damage. Chemokines are also important in angiogenesis and fibrosis and can have anti-inflammatory functions. The study of chemokine biology in transplantation has broadened the understanding of acute and chronic transplant dysfunction. Data suggest that relatively few chemokine receptors play central roles in these developments, and chemokine blockade, either non-selective or specific, has shown promising results in experimental transplantation and is currently being investigated in human trials.