EXPRESSION OF CHEMOKINE GENES DURING REJECTION AND LONG-TERM ACCEPTANCE OF CARDIAC ALLOGRAFTS

Chemokines are cytokines with chemoattractant properties for leukocyte s. They may play a critical role in directing leukocytes to graft site s and in amplifying intragraft inflammation during rejection, Previous studies have tested the intragraft expression of chemokine genes duri ng the rejection of allogeneic skin grafts in mice, In the current stu dy, we used a heterotopic heart transplant model in mice to test the i ntragraft expression of these genes in nonrejecting cardiac isografts, rejecting cardiac allografts, and cardiac allografts that were accept ed due to immunosuppression with gallium nitrate, With the exception o f low levels of interleukin-1 beta and JE, intragraft expression of th e the proinflammatory cytokine genes was not observed in either isogra fts or native heart. Two distinct patterns of chemokine mRNA were obse rved in the rejecting cardiac allografts, Intra-allograft expression o f interleukin-1 beta, interferon-gamma-inducible protein, JE, and KC w as prominent by day 3 after transplantation, The expression of macroph age inflammatory protein (MLP)-1 alpha, MIP-1 beta, and regulated upon activation, normal T cell expressed and secreted (RANTES) was at low or undetectable levels at day 3 after transplantation but at high leve ls by day 8 after transplantation. Sixty days after transplantation, i ntra-allograft expression of chemokines in hearts from gallium nitrate -treated recipients indicated low levels of MIP-1 alpha, MIP-1 beta, a nd RC but high levels of interferon-gamma-inducible protein and RANTES .