DIFFERENTIAL EXPRESSION OF COMPLEMENT C3 AND C4 IN THE HUMAN KIDNEY

Complement activation is associated with a variety of immunologically- mediated renal diseases. Proximal tubular epithelial cells in situ con stitutively express messenger RNA for C4 of the complement system. The se same epithelial cells in culture have been reported to contain mess age for C3 and to secrete this protein when stimulated by IL-2. The pr esent study compared the in situ localization of C3 and C4 message in parallel in a variety of renal biopsy and nephrectomy specimens. All a dequate tissue samples (n = 23) had C4 mRNA throughout in the cortical tubular epithelium. Although C3 message was also expressed in tubular epithelial cells, there was much greater variation in its distributio n. mRNA for C3 was not detected in histologically normal specimens (n = 4) either by in situ or Northern hybridization. Focal C3 message cor related with focal histologic abnormalities (e.g., focal glomeruloscle rosis), while more generalized C3 signal occurred in specimens with mo re diffuse inflammatory processes (e.g., SLE). Infiltrating inflammato ry cells and cells of the glomeruli were uniformly negative for C3 (an d C4) message. Tubular C3 and C4 mRNA appeared to be translated, since selected specimens showed cytoplasmic staining by monoclonal antibodi es to C3c and C4c. These observations are consistent with the hypothes is that local production of inflammatory mediators could induce C3 syn thesis in the renal interstitium, with the possibility that subsequent complement activation could enhance the pathogenic process.