REACTION OF MDCK CELLS TO CRYSTALS OF MONOSODIUM URATE MONOHYDRATE AND URIC-ACID

Madin-Darby canine kidney (MDCK) cells exhibit many of the characteristics of cells of the cortical collecting tubule. Since hypotheses concerning the development of gouty and uric acid nephropathy involve a reaction between such cells and crystals, either of monosodium urate monohydrate (MSUM) or uric acid, the reaction between MDCK cells in culture and the above crystals was studied, both morphologically and functionally. In monolayer cultures, reaction sites developed within four hours of exposure to urate crystals. These increased in number for up to 72 hours and subsided gradually after removal of the crystals. At these reaction sites, crystals were observed to have passed beneath the cell surface and could be demonstrated both within intra-cellular lysosomes as well as within the inter-cellular spaces. When the MDCK cells were maintained as single cells in suspension, phagocytosis of crystals by the majority of the cells could be observed, but the response was much more rapid than in monolayers. During the cell/crystal reaction, significant amounts of lysosomal enzymes and prostaglandin E2 were released and, to a less significant degree, cytosolic enzymes, presumably due to cell lysis. This enzyme release did not occur in MDCK cells grown in protein-free medium, and protein coating of the crystals was necessary for reactivity with cells. In this regard, coating with IgG or lysozyme was more effective than albumin. The reaction with uric acid crystals revealed a reactivity which was lesser in degree but qualitatively similar to that of urate crystals. These studies support the hypothesis that one of the earliest lesions in uric acid or gouty nephropathy occurs between intra-luminal crystals and the epithelial cells of the distal portion of the nephron, and that some of the subsequent renal damage is secondary to this reaction.