Mechanisms of Granulomatous Lung Disease from Inhaled Beryllium: The Role of Antigenicity in Granuloma Formation

Abstract

Granulomatous lung disease is a debilitating and sometimes fatal condition encountered in humans, for which the cellular and molecular mechanisms are poorly understood. Two patterns of granulomatous lung disease are recognized; foreign-body reactions and immune-mediated granulomas. Beryllium inhalation by humans results, in a small number of exposed individuals, in a chronic, granulomatous, immune-mediated pulmonary disease (chronic beryllium lung disease, CBD). Animal models used to study CBD have demonstrated significant species differences in the pathologic response to beryllium. While rats exposed to beryllium appear to develop a chronic, foreign-body response within the lung, dogs so exposed develop beryllium-specific immune responses within the lung and blood, accompanied by immune granulomas within the lung. At the heart of this difference appears to be the ability of the dog, but not the rat, to immunologically recognize the antigenicity of beryllium. This important difference further underscores the need to understand the mechanistic differences among similar disease syndromes, particularly if therapeutic regimens are to be used.