EXPRESSION OF DECAY-ACCELERATING FACTOR MESSENGER-RNA AND COMPLEMENT C3 MESSENGER-RNA IN HUMAN DISEASED KIDNEY

Background. Decay accelerating factor (DAF), a product of mesangial ce lls in vitro, is expressed on the surface of cells and is a candidate for the focal suppression of complement activation. It is not clear at present whether the levels of expression of DAF and intrarenal C3 syn thesis correlate with the level of tissue injury. Methods. Immunohisto chemistry for DAF and C3 and nonradioactive in situ hybridization with digoxigenin-labeled oligonucleotide probe for DAF and C3 mRNA were pe rformed in 22 tissue samples of kidneys from patients with IgA nephrop athy (IgAN), 6 with membranous nephropathy (MN), 6 with lupus nephriti s (LN), and five normal kidneys. Results. In the normal kidney, DAF wa s confined to the juxtaglomerular apparatus and little or no C3 was de tected; however, a few glomerular cells were positive for DAF mRNA but no C3 mRNA positive cells were detected. In diseased kidneys, DAF and C3 as well as their mRNAs were detected in mesangial cells, tubular c ells and infiltrating cells. Glomerular epithelial cells and Bowman's capsule cells contained little or no DAF and C3 but were positive for their mRNAs. The mean percentages of mesangial cells positive for DAF and C3 mRNAs were 49.3 +/- 11.5% and 50.7 +/- 10.3% in IgAN, and 17.0 +/- 6.3% and 19.4 +/- 9.0% in MN, respectively. The percentage of mesa ngial cells positive for DAF and C3 mRNAs among intraglomerular cells correlated positively with the degree of mesangial proliferation and g lomerular sclerosis in IgAN. In contrast, in LN the percentage of glom erular cells positive for DAF mRNA correlated negatively with the degr ee of glomerular injury, while the percentage of cells positive for C3 mRNA did not change with the progression oi the disease. The ratio of C3 mRNA/DAF mRNA of glomerular cells correlated with the degree of gl omerular injury in both IgAN and LN. In the tubulointerstitium, the pe rcentage of cells expressing mRNA, and C3 mRNA/DAF mRNA ratio correlat ed with the degree of tubular atrophy and interstitial broadening in b oth IgAN and LN. Conclusions. We conclude that DAF and C3 mRNAs are sy nthesized in human diseased kidneys, and that a balance between locall y synthesized DAF and C3 may be important in the progression of glomer ulonephritis.