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Glomerular tissue factor expression in crescentic glomerulonephritis. Correlations between antigen, activity, and
P G Tipping1, J H Erlich, J Apostolopoulos
1Department of Medicine, Monash University, Monash Medical Centre, Clayton, Victoria, Australia.
The American Journal of Pathology
|December 1, 1995
Summary
Tissue factor (TF) activity increases early in crescentic glomerulonephritis, initially from intrinsic cells. Later, infiltrating macrophages synthesize TF, leading to increased urinary TF excretion and glycosylation.
Area of Science:
- Nephrology
- Immunology
- Pathology
Background:
- Crescentic glomerulonephritis (GN) involves glomerular inflammation.
- Tissue Factor (TF) plays a role in coagulation and inflammation.
- Understanding TF expression in GN is crucial for disease mechanisms.
Purpose of the Study:
- To investigate the correlation between glomerular TF activity, antigen, and mRNA localization in experimental crescentic GN.
- To elucidate the cellular sources and temporal changes of TF during GN progression.
Main Methods:
- Induction of crescentic GN in rabbits.
- Measurement of glomerular TF activity, TF antigen levels, and TF mRNA expression.
- Assessment of cellular infiltration, particularly macrophages.
- Analysis of TF molecular weight and urinary TF excretion.
Main Results:
- Glomerular TF activity and antigen increased early in GN, preceding significant TF mRNA elevation.
- TF mRNA colocalized with macrophages during peak infiltration, with increased expression.
- Glomerular TF showed increased molecular weight due to glycosylation, and urinary TF excretion was elevated.
- TF activity and antigen decreased in glomeruli later, while urinary TF and glomerular TF mRNA remained high.
Conclusions:
- Early TF activity in GN is primarily due to functional upregulation in intrinsic glomerular cells.
- In advanced GN, infiltrating macrophages become the main source of TF synthesis.
- Increased TF glycosylation and urinary shedding indicate significant glomerular TF turnover in later stages of GN.