EPITHELIAL-DERIVED NEUTROPHIL-ACTIVATING FACTOR-78 PRODUCTION IN HUMAN RENAL TUBULE EPITHELIAL-CELLS AND IN RENAL-ALLOGRAFT REJECTION

Chemotactic cytokines, or chemokines, are likely mediators of inflamma tory cell recruitment in renal allograft rejection. A recent addition to the C-X-C super gene family branch of chemokines is epithelial-deri ved neutrophil-activating factor-78 (ENA-78). ENA-78 is a 78-amino aci d peptide with neutrophil-activating and chemotactic properties. This chemokine is unique in that it was originally isolated and cloned from an IL-1-stimulated human pulmonary epithelial cell line, A549. In thi s article, we investigated whether ENA-78 could be produced by human r enal epithelial cells. We found that primary cultures of human renal c ortical epithelial cells with tubular cell attributes could express si gnificantly increased steady state levels of ENA-78 mRNA when stimulat ed with IL-1 beta (2.0 ng/ml). In addition, these cells also secreted significantly increased ENA-78 antigen compared with controls when sti mulated with IL-1 beta (2.0 ng/ml). Other proinflammatory agonists, in cluding TNF alpha, IFN gamma, and LPS failed to stimulate ENA-78 stead y state mRNA or antigenic peptide production by renal cortical epithel ial cells. In addition, biopsy tissue from acutely rejecting human ren al allografts had higher copy number of ENA-78 mRNA compared with nonr ejecting renal allograft controls using a quantitative reverse transcr iptase polymerase chain reaction method with a mutant ENA-78 transcrip t. In the proinflammatory milieu of the rejecting renal allograft, IL- 1 beta produced by host and donor mononuclear cells may drive ENA-78 p roduction by allograft tubule cells, thus effecting leukocyte recruitm ent into the tubulointerstitial compartment.