title: Experimentally induced hyperoxaluria in MCP-1 null mice.
abstract: Experimental animal model studies suggest that calcium oxalate (CaOx) crystal deposition in the kidneys is associated with the development of oxidative stress, epithelial injury and inflammation. There is increased production of inflammatory molecules including osteopontin (OPN), monocyte chemoattractant protein-1 (MCP-1) and various subunits of inter-alpha-inhibitor such as bikunin. What does the increased production of such molecules suggest? Is it a cause or consequence of crystal deposition? We hypothesized that over-expression and increased production of MCP-1 is a result of the interaction between renal epithelial cells and CaOx crystals after their deposition in the renal tubules. We induced hyperoxaluria in MCP-1 null as well as wild type mice and examined pathological changes in their kidneys and urine. Both wild type and MCP-1 null male mice became hyperoxaluric and demonstrated CaOx crystalluria. Neither of them developed crystal deposits in their kidneys. Both showed some morphological changes in their renal proximal tubules. Significant pathological changes such as cell death and increased urinary excretion of LDH were not seen. Results suggest that at least in mice (1) Increase in oxalate and decrease in citrate excretion can lead to CaOx crystalluria but not CaOx nephrolithiasis; (2) MCP-1 does not play a role in crystal retention within the kidneys; (3) Expression of OPN and MCP-1 is not increased in the kidneys in the absence of crystal deposition; (4) Crystal deposition is necessary for significant pathological changes and movement of monocytes and macrophages into the interstitium.
authors.affiliation: Department of Pathology, Immunology and Laboratory Investigation, College of Medicine, University of Florida, Box 100275, Gainesville, FL 32610, USA. Khan@pathology.ufl.edu
authors.forename: Saeed R
authors.initials: SR
authors.lastname: Khan
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Glenton
mesh_terms: D000818:Animals; D002129:Calcium Oxalate / Q000378:metabolism; D018932:Chemokine CCL2 / Q000235:genetics / Q000502:physiology*; D003460:Crystallization; D004195:Disease Models, Animal; D005260:Female; D006959:Hyperoxaluria / Q000209:etiology* / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053040:Nephrolithiasis / Q000209:etiology* / Q000235:genetics
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D002129:Calcium Oxalate