Cytokine production induced by binding and processing of calcium oxalate crystals in cultured macrophages

Deposition of calcium oxalate (CaOx) crystals in the renal interstitium is common in humans with primary oxalosis and secondary hyperoxaluria, as well as in kidneys of rats with CaOx nephrolithiasis. In vivo, macrophages and multinucleated giant cells mostly encapsulate these crystals. To investigat e whether macrophages are able to dispose of CaOx crystals after phagocytos is, we used a nontransformed macrophage cell line derived from mouse spleen progenitors. Cytokine assays showed that in response to crystal binding an d phagocytosis, these macrophages release tumor necrosis factor-alpha. This release was evident at 8 hours, maximal at 24 hours, and decreased to cont rol values after 48 hours of incubation with crystals. A very low but signi ficant release of interleukin-6 into the culture medium was only noticed af ter 32 hours. Radiochemical experiments showed that these cells bind 38.8% of the CaOx crystals added. After 4 days, all internalized crystals had bee n dissolved and their molecular constituents released into the extracellula r environment. Confocal laser scanning microscopy followed by morphometrica l analyses confirmed these results. Long-term (survival) analyses showed th at in the interval under study and at the crystal doses used, cell viabilit y was not significantly affected. These findings support the view that prop erly functioning macrophages are able to remove CaOx deposits from the rena l interstitium and that these cells produce inflammatory cytokines before c rystal dissolution. (C) 2001 by the National Kidney Foundation, Inc.