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Updated: Aug 15, 2026
Phenotypic Characterization of Macrophages from Rat Kidney by Flow Cytometry
Published on: October 18, 2016
Monocytes and macrophages in focal glomerulosclerosis in Zucker rats
1Department of Pathology, University of British Columbia, Vancouver, Canada.
Abstract:
It has been recently suggested that focal glomerulosclerosis (FGS) is analogous to atherosclerosis. Obese Zucker (OZ) rats spontaneously develop hyperlipidemia, proteinuria and FGS. To evaluate the role of the monocyte (MO) and its derivatives in the pathogenesis of the lesion, 30 OZ rats and 15 lean littermates (LZ) were followed for up to 240 days of age. At 75, 120 and 240 days of age, groups of 10 OZ and 5 LZ were assessed with respect to serum total and free cholesterol (TC and FC), triglyceride, lipoprotein electrophoresis, renal histology, histochemistry and immunohistochemistry. All serum lipids were raised at 75 days in OZ rats and increased progressively at 120 and 240 days. The early lesions of FGS were first demonstrated in OZ at 120 days with more advanced lesions at 240 days. FGS was seen in LZ only at 240 days when their serum lipids were raised. Intraglomerular MO infiltration was significantly higher in OZ than in LZ at all time periods (p less than 0.01) and greater in glomeruli with FGS lesions than in those without (p less than 0.01 and 120 days and p less than 0.05 at 240 days). Staining for ED1 and Ia antigens with monoclonal antibodies demonstrated increasing numbers of intraglomerular ED1+ and Ia+ cells with increasing age and extent of FGS. The findings suggest a role for intraglomerular macrophages in the pathogenesis of FGS in OZ.
Insights
Monocyte infiltration plays a key role in focal glomerulosclerosis (FGS) development in obese Zucker rats. These findings highlight the involvement of macrophages in FGS pathogenesis.
Area of Science:
- Nephrology
- Immunology
- Pathology
Background:
- Focal glomerulosclerosis (FGS) pathogenesis is increasingly linked to processes similar to atherosclerosis.
- Obese Zucker (OZ) rats exhibit spontaneous hyperlipidemia, proteinuria, and FGS, serving as a relevant model.
- The role of monocytes (MO) and their derivatives in FGS lesion development requires further elucidation.
Purpose of the Study:
- To investigate the role of monocytes and their derivatives in the development of focal glomerulosclerosis (FGS) in Obese Zucker (OZ) rats.
- To compare intraglomerular monocyte infiltration and macrophage markers in OZ rats versus lean littermates (LZ) over time.
Main Methods:
- Longitudinal study of 30 OZ rats and 15 lean littermates (LZ) up to 240 days of age.
- Assessment of serum lipids, lipoprotein electrophoresis, renal histology, histochemistry, and immunohistochemistry at 75, 120, and 240 days.
- Quantification of intraglomerular monocyte infiltration using ED1 and Ia antigen staining with monoclonal antibodies.
Main Results:
- Obese Zucker rats showed elevated serum lipids from 75 days, progressing with age.
- Early FGS lesions were observed in OZ rats at 120 days, with advanced lesions at 240 days.
- Significantly higher intraglomerular monocyte infiltration was found in OZ rats compared to LZ rats at all time points, correlating with FGS severity.
Conclusions:
- Intraglomerular monocyte infiltration, particularly macrophages expressing ED1 and Ia antigens, is significantly increased in Obese Zucker rats with FGS.
- These findings strongly suggest a crucial role for intraglomerular macrophages in the pathogenesis of focal glomerulosclerosis in this obese model.
