Cytological characterization of apatitic calcium phosphate structures in bronchial epithelial tissue cultured from a child with cystic fibrosis (ΔF508)

Abstract

Patients with cystic fibrosis homozygous for the AF508 mutation have marked disturbances in ion exchanges in a variety of tissues. Alterations in intra- or extracellular levels of Ca2+ and calcifications have been observed in numerous tissues from such patients, although the nature and origin of such calcifications have yet to be elucidated. In this study, we investigated the formation of calcifications in the respiratory tract of a AF508 homozygous child and attempted to establish their origin. Samples of bronchial epithelium from this patient were subjected to cytophysiological analysis ex vivo and in vitro. The defect of targeting of the cystic fibrosis transmembrane conductance regulator (CFTR) to the apical plasma membrane of epithelial cells was verified. Cytochemical and ultrastructural analysis revealed the presence of crystalline aggregates in fine needles in the respiratory tract. Cytochemical analysis, X-ray spectrometry, and electron diffraction showed that these aggregates corresponded to crystals of calcium phosphate in an apatite-like structure. Ultrastructural study of primary cultures of bronchial epithelium showed the presence of calcium phosphate crystals in granules from Golgi apparatus and in mitochondria. These observations indicated that modifications of ionic exchanges due to a defect in targeting of CFTR AF508 to the apical plasma membrane led to the formation of crystals of calcium phosphate in the cytoplasm of pulmonary cells. These crystals could enhance inflammation of the lung in patients with cystic fibrosis.

Response of Vicia faba L. to metal toxicity on mine tailing substrate: Geochemical and morphological changes in leaf and root

“…They were found as clusters of needle-like crystals surrounded by amorphous material. EDX and electronic diffraction analysis showed that they were Ca-P crystals close to apatite composition (Table 5), which have already been described generally in pathological cases of animal tissues (Hering et al, 1987;Hollande et al, 1990;Cantet et al, 2001). To our knowledge, calcium phosphate crystals have not yet been described in plants.…”

Characterization of Granulations of Calcium and Apatite in Serum as Pleomorphic Mineralo-Protein Complexes and as Precursors of Putative Nanobacteria

“…On the other hand, the low crystallinity may also correspond to the presence of carbonate substitutions in the crystal lattice [49]. Diffraction patterns with similar fuzzy concentric rings were also observed in dentin [64] and calcified cartilage [65], as well as in tissues undergoing extraskeletal calcification [66], which were also interpreted as the presence of HAP possessing a low degree of crystallinity. As a further reference, diffraction patterns of the mineral precursor in bones produced amorphous diffraction patterns while more mature bone harbored both fuzzy rings and dots similar to the more crystalline patterns obtained for some of our serum granulations [67].…”

Lung parenchymal calcifications in a child with cystic fibrosis

“…The authors hypothesized that the calcium was possibly sequestered by mitochondria and Golgi apparatus partly due to an increase in electron transport chain activity. 7 We believe the parenchymal calcifications found in this case signify ongoing chronic inflammation consistent with the dystrophic type of lung calcifications. The lack of causative organism or hamartoma raises the question if this is an inherent property of CF.…”

“…Extensive parenchymal calcification as in our child has never been previously reported. Cantet and colleagues 7 reported seeing crystalline structures on cytological analysis of lung tissue from a patient with CF following lobectomy which were likely to be calcium phosphate deposits. 7 It is unclear if the calcification was seen macroscopically in that case.…”

“…Cantet and colleagues 7 reported seeing crystalline structures on cytological analysis of lung tissue from a patient with CF following lobectomy which were likely to be calcium phosphate deposits. 7 It is unclear if the calcification was seen macroscopically in that case. The authors hypothesized that the calcium was possibly sequestered by mitochondria and Golgi apparatus partly due to an increase in electron transport chain activity.…”