Transplantation chemokines

Chemokines have been shown to be associated with a number of autoinflammatory diseases including multiple sclerosis, rheumatoid arthritis, atherosclerosis, dermatitis, and organ transplant rejection. Evidence, reviewed below, is mounting that chemokines may play a major role in the pathophysiology of these diseases and thus chemokine receptor antagonists could prove to be useful therapeutics in treating these and other proinflammatory diseases. 

Key Words Allograft transplantation chemokine receptor acute rejection chronic rejection CCR1 CCR5 CXCR3 CXCR1 CXCR2. 

The literature on chemokines in transplantation has been extensively reviewed in recent years (7-9). In this chapter, we focus on a limited number of chemo-kine receptors where evidence for a functional role has been verified. From the plethora of chemokine receptors, this has been demonstrated for CXCR1/2 in reperfusion injury and for CCR1, CCR5, and CXCR3 during acute and chronic allograft rejection. 

Before examining the potential roles of chemokines in the pathophysiology of transplant rejection, it is important to review the biology that underlies the rejection of solid organ allografts. 

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Horuk R, Clayberger C, Krensky AM, et al. A non-peptide functional antagonist of the CCR1 chemokine receptor is effective in rat heart transplant rejection. J Biol Chem 2001 276 4199-4204. 

Vassalli G, Simeoni E, Li JP, Fleury S. Lentiviral gene transfer of the chemokine antagonist RANTES 9-68 prolongs heart graft survival. Transplantation 2006 81 240-246. 

Segerer S, Cui Y, Eitner F, et al. Expression of chemokines and chemokine receptors during human renal transplant rejection. Am J Kidney Dis 2001 37 518-531. 

Pattison J, Nelson PJ, Huie P, et al. RANTES chemokine expression in cell-mediated transplant rejection of the kidney. Lancet 1994 343 209-211. 

Fischereder M, Luckow B, Hocher B, et al. CC chemokine receptor 5 and renal-transplant survival. Lancet 2001 357 1758-1761. 

Hoffmann U, Segerer S, Rummele P, et al. Expression of the chemokine receptor CXCR3 in human renal allografts—a prospective study. Nephrol Dial Transplant 2006 21 1373-1381. 

Hu H, Aizenstein BD, Puchalski A, Burmania JA, Hamawy MM, Knechtle SJ. Elevation of CXCR3-binding chemokines in urine indicates acute renal-allograft dysfunction. Am J Transplant 2004 4 432M37. 

Segerer S, Regele H, Mack M, et al. The duffy antigen receptor for chemokines is up-regulated during acute renal transplant rejection and crescentic glomerulonephritis. Kidney Int 2000 58 1546-1556. 

Abdi R, Tran TB, Sahagun-Ruiz A, et al. Chemokine receptor polymorphism and risk of acute rejection in human renal transplantation. J Am Soc Nephrol 2002 13 754-758. 

CTCE-0214 Chemokine Therapeutics Phase II Stem cell transplantation 111, 112... 

Yun JJ, Fischbein MP, Laks H, et al. Early and late chemokine production correlates with cellular recruitment in cardiac allograft vasculopathy. Transplantation 2000 69(12) 2515-2524. 

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