Lymphotactin: akeyregulator oflymphocyte trafficking during acutegraft rejection

SUMMARY Theattraction ofleucocytes toallografts isessential forrejection. Theprcocessiscontrolled by chemokines. Inorder toclarify therole oflymphotactin (acytokine that represents anovel branch ofthechemokine superfamily) inregulating leucocyte trafficking during graft rejection, we used ratrenal transplantation models toexamine its geneexpression andthedistribution oflymphotactin-expressing cells inrenal grafts. Lymphotactin mRNA was upregulated strongly inacutely rejecting renal allografts. ThemRNA was undetectable inisografts, chronically rejecting renal allografts or normalkidney. Oncelymphotactin was expressed, large numbersofinfiltrating lymphocytes were seen.Moreover extended studies demonstrated thatincultured ratspleen cells theexpression oflymphotactin mRNA was markedly induced byphytohaemagglutinin (PHA)or phorbol myristate acetate (PMA),andsuchinduction was inhibited bytheimmunosuppressive drugs FK506andcyclosporin. Collectively, these observations provide new evidence demonstrating thatlymphotactin isa keyregulator oflymphocyte motility andadhesiveness during acute allograft rejection. FK506andcyclosporin inhibition oflymphotactin expression islikely to represent an important molecular mechanism oftheaction ofthedrugs.

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