Cell Biology – Immunology – Pathology
Kidney International (1998) 54, 120–130; doi:10.1046/j.1523-1755.1998.00961.x
Expression of decay accelerating factor mRNA and complement C3 mRNA in human diseased kidney
Katsushige Abe, Masanobu Miyazaki, Takehiko Koji, Akira Furusu, Yoshiyuki Ozono, Takashi Harada, Hideto Sakai, Paul K Nakane and Shigeru Kohno
The Second Department of Internal Medicine, Third Department of Anatomy, and Division of Renal Care Unit, Nagasaki University School of Medicine, Nagasaki; and Department of Nephrology, Tokai University, Kanagawa, Japan
Correspondence: Katsushige Abe, M.D. and Masanobu Miyazaki, M.D. and Ph.D., The Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. E-mail: rukonyan@ga2.so-net.ne.jp
Received 23 September 1997; Revised 21 January 1998; Accepted 28 January 1998.
Abstract
Expression of decay accelerating factor mRNA and complement C3 mRNA in human diseased kidney.
Background
Decay accelerating factor (DAF), a product of mesangial cells 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 synthesis correlate with the level of tissue injury.
Methods
Immunohistochemistry for DAF and C3 and nonradioactive in situ hybridization with digoxigenin-labeled oligonucleotide probe for DAF and C3 mRNA were performed in 22 tissue samples of kidneys from patients with IgA nephropathy (IgAN), 6 with membranous nephropathy (MN), 6 with lupus nephritis (LN), and five normal kidneys.
Results
In the normal kidney, DAF was confined to the juxtaglomerular apparatus and little or no C3 was detected; 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 cells 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 mesangial cells positive for DAF and C3 mRNAs among intraglomerular cells correlated positively with the degree of mesangial proliferation and glomerular sclerosis in IgAN. In contrast, in LN the percentage of glomerular cells positive for DAF mRNA correlated negatively with the degree of glomerular injury, while the percentage of cells positive for C3 mRNA did not change with the progression of the disease. The ratio of C3 mRNA/DAF mRNA of glomerular cells correlated with the degree of glomerular injury in both IgAN and LN. In the tubulointerstitium, the percentage of cells expressing mRNA, and C3 mRNA/DAF mRNA ratio correlated with the degree of tubular atrophy and interstitial broadening in both IgAN and LN.
Conclusions
We conclude that DAF and C3 mRNAs are synthesized in human diseased kidneys, and that a balance between locally synthesized DAF and C3 may be important in the progression of glomerulonephritis.
Keywords:
DAF, complement C3, in situ hybridization, glomerulonephritis, injury, mRNA, progression of renal injury
Abbreviations:
C/D, the ratio between the percentage of complement C3 mRNA-positive cells and percentage of DAF mRNA-positive cells per glomerulus and interstitial field; DAF, decay accelerating factor; DIG, digoxigenin; DPLN, diffuse proliferative lupus nephritis; e%C, percentage of epithelial cells positive for C3 mRNA among intraglomerular cells; e%C/e%D, C/D in epithelial cells; e%D, percentage of epithelial cells positive for DAF mRNA among intraglomerular cells; g%C, percentage of glomerular cells positive for C3 mRNA among intraglomerular cells; g%C/g%D, C/D in glomerular cells; g%D, percentage of glomerular cells positive for DAF mRNA among intraglomerular cells; HRP, horseradish peroxidase; i%C, percentage of infiltrating cells positive for C3 mRNA among total infiltrating cells; i%C/i%D, C/D in infiltrating cells; i%D, percentage of infiltrating cells positive for DAF mRNA among total infiltrating cells; IgA, immunoglobulin A; IgAN, IgA nephropathy; IgAN-I, IgAN with minimal-to-mild lesions; IgAN-II, IgAN with moderate-to-advanced lesions; JGA, juxtaglomerular apparatus; LN, lupus nephritis; mesLN, mesangial proliferative lupus nephritis; m%C, percentage of mesangial cells positive for C3 mRNA among intraglomerular cells; m%C/m%D, C/D in mesangial cells; m%D, percentage of mesangial cells positive for DAF mRNA among intraglomerular cells; MN, membranous nephropathy; t%C, percentage of tubules positive for C3 mRNA among total number of tubules; t%C/t%D, C/D ratio in tubules; t%D, percentage of tubules positive for DAF mRNA among total number of tubules
