Biochemical characterization of endogenously formed eosinophilic crystals in the lungs of mice

Crystals seldom form spontaneously within tissues of mammals, except in the urinary tract or in association with eosinophil-rich diseases in humans (C harcot-Leyden crystals). Endogenously formed eosinophilic: crystals have be en reported in respiratory tract and other tissues of several strains of mi ce, but the biochemical characterization of these crystals has not been rep orted. In this study, eosinophilic crystal formation was examined in homozy gous C57BL/6J viable motheaten mice, lung-specific surfactant apoprotein G promoter/soluble human tumor necrosis factor p75 receptor type II fusion pr otein transgenic mice (C57BL/6NTac x Sv/129), and CD40L-deficient mice with spontaneous Pneumocystis carinii infection. In viable motheaten but not wi ld type mice, rapidly developing crystals represented a major feature of th e fatal lung injury induced by macrophage dysregulation. Conversely, eosino philic crystals did not form until 4-8 months of age in transgenic and CD40 L-deficient mice and were present in 10-30% of age-matched wild type contro ls. Mass spectrometry analysis of proteins from bronchoalveolar lavage flui d identified the crystals as Ym1, sometimes referred to as T-lymphocyte-der ived eosinophil chemotactic factor. The Ym1 sequence was homologous to chit inase, and enzymatic assays indicated a 3-5-fold increase in chitinase acti vity compared with control mice. Intracellular and extracellular crystals a ssociated with epithelial damage suggested that the crystals may contribute to lung inflammation through mechanical damage and enzymatic degradation.