Localization of C-X-C and C-C chemokines to renal tubular epithelial cellsin human kidney transplants is not confined to acute cellular rejection

Chemokines are important mediators of leucocyte chemoattraction to inflamma tory sites. Previous work has shown that the expression of some chemokines is upregulated during renal transplant rejection. The objectives of the pre sent study were to determine whether chemokine expression is increased duri ng renal transplant rejection. Immunohistochemistry was used to localize th e C-X-C (cc) chemokine interleukin-8 (IL-8) and the C-C (beta) chemokines m onocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory prote in-1 beta (MIP-1 beta) in 30 needle biopsies of human kidney transplants ta ken for diagnosis of renal dysfunction. Urine samples from transplant patie nts taken immediately prior to biopsy were assayed for chemokine content us ing enzyme-linked immunosorbent assays (ELISAs). Results from groups of pat ients having different clinicopathological diagnoses were then compared. Al l three chemokines were detected in most renal transplant biopsies showing acute cellular rejection but, although infiltrating leucocytes were often p ositive, staining was predominantly localized to renal tubular epithelium. Staining for MCP-1 was generally weaker than for the other chemokines, and collecting tubules were usually stained more strongly than proximal convolu ted tubules. Tubular epithelial staining was also found in biopsies from pa tients without signs of acute cellular rejection. There were significantly higher amounts of IL-8 in the urine of patients with acute cellular rejecti on, even when patients with urinary tract infections were excluded, but mea n titres of urinary MIP-1 beta did not differ between patient groups. This was also found when titres were normalized for urine volume and creatinine levels. Production of IL-8, MCP-1 and MIP-1 beta is not confined to kidney transplants showing acute cellular rejection, and may be a relatively nonsp ecific response of tubular epithelial cells to renal damage.