Expression of cyclooxygenase-2 in biopsies obtained from human transplanted kidneys undergoing rejection.

BACKGROUND

The inducible cyclooxygenase (COX)-2 is a target of immunosuppressive drugs routinely administered to patients after transplantation. This study investigates a potential involvement of COX-2 in transplant rejection. Therefore, we examined the expression of COX-2 in biopsies obtained for diagnostic purposes.

METHODS

COX-2 was detected by immunohistochemistry and in situ hybridization. Congruent staining was obtained by both methods: in specimens of a kidney explanted as the result of vascular rejection, tubular epithelial cells and endothelial cells stained positively for COX-2. Furthermore, in appendiceal specimens obtained at surgery, epithelial cells of the crypts, interstitial cells, and mesothelial cells were positive by both methods, affirming the specificity of the antibody.

RESULTS

Compared with healthy control subjects, intensive staining of COX-2 was observed in most of the 28 biopsies obtained from patients diagnosed with vascular rejection combined with cellular interstitial rejection and tubulitis. Glomeruli and the macula densa area were essentially negative compared with prominent staining in cortical and medullary epithelial cells of the tubuli. Staining was distinct with individual positive cells in the tubular cross sections. Few arteries expressed COX-2 in intimal cells. Less prominent expression of COX-2 was detected in the biopsies of six kidneys obtained from patients diagnosed with acute tubular necrosis.

CONCLUSION

This is the first report to show the up-regulation of COX-2 in human transplanted kidneys, despite ongoing immunosuppressive treatment. It remains to be established whether the up-regulation of COX-2 is part of the rejection process or has to be considered implicated in renal preservative mechanisms.