Expression of tumor necrosis factor receptors in normal kidney and rejecting renal transplants

Activation of the TNF signal transduction cascade is initiated by the inter action of TNF with either of two cell surface receptors, TNFR-1 and TNFR-2. The levels and regulation of expression of these two receptors has been ex tensively analyzed in cultured cells, but little is known of TNFR expressio n in situ. We analyzed the expression of TNFR-1 and -2 in normal human rena l kidney and in renal transplants undergoing acute cellular rejection. Immu nohistochemistry and immunogold electron microscopy indicated a strong expr ession of TNFR-1 on the endothelium of glomeruli of normal kidney. Immunogo ld colocalization for TNFR-1 and a marker of the trans-Golgi network (TGN-4 6) demonstrated TNFR-1 within the Golgi complex in endothelial cells in nor mal kidney, confirming our previous studies with cultured cells. TNFR-1 exp ression was lost in glomeruli from acutely rejecting kidney, but TNFR-1 was detected in abundance on infiltrating leukocytes in the interstitium of al lografts with acute rejection. In contrast, TNFR-2 was demonstrated predomi nantly in epithelia[ cells of distal convoluted tubule (DCT) in acute rejec tion kidney near TNF-expressing leukocytes. TNF was absent in normal kidney , but present in rejecting allograft. TNF was found in infiltrating leukocy tes and in adjacent tubular epithelia[ cells. In situ hybridization showed TNFR-1 mRNA within the endothelium of the glomeruli and of a few arterioles in normal kidney, whereas TNFR-2 mRNA was seen in tubular epithelial cells of the DCT in acute transplant rejection. These data reveal that there is both differential expression and regulation of the two TNF receptors in hum an kidney.