Calcium oxalate and iron accumulation in sarcoidosis

Background: In many patients with sarcoidosis, the granulomas contain inclu sion bodies within giant cells. Many giant cells contain crystalline oxalat e that chemically coordinates iron on the surface of the crystal. If this i ron is incompletely coordinated and capable of redox cycling, then oxalate might contribute to granuloma formation in the lung. Methods: Using human t issues, isolated alveolar macrophages and respiratory epithelial cells, we measured the ability of calcium oxalate to sequester iron, stimulate cytoki ne release and cause granuloma formation. We then studied the effects of in vivo oxalate instillation on pulmonary granuloma formation over 3 to 6 mon ths in rats. Results: Calcium oxalate present in human sarcoid granulomas s equesters significant amounts of iron and ferritin. In alveolar macrophage cultures, oxalate accumulates iron and stimulates ferritin production and g iant cell formation. In cultured respiratory epithelial cells, calcium oxal ate increases the release of two interleukins (IL), IL-8 and IL-6, involved in granuloma formation by 8 to 10 fold within 24 hours. Intratracheal inst illation of calcium oxalate crystals into the lungs of rats is associated w ith pulmonary iron and ferritin accumulation and organic carbonyl formation consistent with sustained oxidative stress. These exposures were accompani ed by influx of alveolar macrophages, giant cell formation, and a granuloma tous response in the lung. Conclusions: These results support an associatio n between calcium oxalate deposition in the lung, iron mediated oxidative s tress and formation of some of the granulomas of sarcoidosis.