Early increased chemokine expression and production in murine allogeneic skin grafts is mediated by natural killer cells

Background Increased expression of chemokine mRNA is observed in allogeneic but not syngeneic skin grafts 3-4 days aft:er transplantation. The recipie nt cells mediating this early inflammatory response in allografts remain un identified, Methods. Isogeneic and allogeneic skin grafts were transplanted to euthymic and athymic nude mice. mRNA expression and protein production of macrophag e inflammatory protein-1 alpha (MIP-1 alpha), MIP-1 beta, and the murine ho molog of Gro alpha, i.e. KC, from graft homogenates retrieved 3-4 days post transplantation was tested by Northern blot hybridization and ELISA. To dep lete NK cells, recipients were treated with anti-asialo GM1 (ASGM1) antiser a or with anti-NK1.1 mAb before transplantation. Results. Express:ion of KC, MIP-1 alpha, and MIP-1 beta mRNA was equivalent in C57BL/6 allogeneic skin grafts and BALB/c isografts at day 2 posttransp lant. At day 3 posttransplant, chemokine mRNA levels decreased in isografts but were maintained at high levels in the allografts. Increased early chem okine mRNA was also observed in C57BL/6, but not BALB/c(++) grafts on BALB/ c athymic(nu/nu) recipients. Treatment of allograft recipients with ASGM1 o r with anti-NK1.1 antibody eliminated NM cells from the spleen and allograf t infiltrating cell populations and decreased early chemokine mRNA levels i n allografts 60-70%, Analyses of allograft homogenates indicated increased levels of KC, MIP-l alpha, and MIP-1 beta protein at day 4 posttransplant t hat were decreased in recipients depleted of NR cells, Early chemokine mRNA levels were equivalent in isogeneic and semiallogeneic Fl grafts. Conclusions, Early chemokine mRNA expression and protein production in allo geneic skin grafts is amplified by recipient natural killer (NM) cells. The se results indicate a novel. function for infiltrating NK cells in mediatin g early increased intra-allograft chemokine production and inflammation dur ing the initiation of acute rejection.