Role of macrophages and colony-stimulating factor-1 in murine antiglomerular basement membrane glomerulonephritis

• Published in: Journal of the American Society of Nephrology Vol. 5; no. 11; pp. 1903 - 1909
• Main Authors: Neugarten, J, Feith, G W, Assmann, K J, Shan, Z, Stanley, E R, Schlondorff, D
• Format: Journal Article
• Language: English
• Published: United States 01-05-1995
• Subjects: Animals; Antibodies; Autoantibodies; Basement Membrane - immunology; Chemokine CCL5; Chemotactic Factors - genetics; Chemotactic Factors - physiology; Colony-Stimulating Factors - genetics; Colony-Stimulating Factors - physiology; Cytokines - genetics; Cytokines - physiology; Disease Models, Animal; Fluorescent Antibody Technique; Glomerulonephritis - pathology; Kidney Glomerulus - immunology; Kidney Glomerulus - pathology; Lymphokines - genetics; Macrophages - physiology; Mice; Mice, Mutant Strains; Monocyte Chemoattractant Proteins; RNA, Messenger - analysis; T-Lymphocytes - metabolism
• ISSN: 1046-6673
• DOI: 10.1681/ASN.V5111903

Macrophages have been shown to mediate glomerular injury in antiglomerular basement membrane (anti-GBM) glomerulonephritis in rats and rabbits. To evaluate the role of macrophages and the macrophage-related cytokines, colony stimulating factor-1 (CSF-1), monocyte chemoattractant protein-1 (MCP-1) and RANTES, accelerated anti-GBM nephritis was studied in op/op mutant mice, which lack CSF-1 and are severely macrophage deficient, and in heterozygous op/+ control mice. Observations were made 24 h and 3 days after the injection of rabbit anti-mouse GBM antibody in mice preimmunized with rabbit immunoglobulin G. Proteinuria rose progressively in both groups but did not differ between them (urine protein/creatinine ratio at 3 days: 1.01 +/- 0.38 in op/op versus 1.45 +/- 0.43 in op/+; P, not significant). In both op/op and op/+ mice, anti-GBM nephritis was associated with renal expression of mRNA for RANTES and MCP-1 and barely detectable levels of mRNA for CSF-1. In contrast, these cytokines were not expressed in sham-injected mice. Morphologic lesions appeared earlier in op/op mice but were comparable by Day 3. Glomerular injury consisted of capillary thrombosis and endothelial cell damage associated with mild to moderate leukocyte infiltration. Despite enhanced expression of mRNA for RANTES and MCP-1, glomerular macrophage infiltration was not increased in op/+ mice. It was concluded that, in mice, in contrast to rats and rabbits, accelerated anti-GBM nephritis may develop in the absence of both CSF-1 and macrophage infiltration.