Alveolar Proteinosis and Phospholipidoses of the Lungs

Hook, Gary E. R.

doi:10.1177/0192623391019004-116

Cited by 32 publications

(48 citation statements)

References 219 publications

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“…The improvement of symptoms with surfactant administration in this infant and in another child with TTF-1 deficiency (7) is clinical evidence supporting a surfactant abnormality component. In contrast to genetic disorders of surfactant function (i.e., SP-B and ABCA3 deficiencies), wherein lamellar bodies are reduced, absent, or abnormally formed (30)(31)(32)(33), or alveolar proteinosis, wherein there is accumulation of phospholipid membranes and abnormal tubular myelin (34), the ultrastructure of the lamellar bodies in this infant appeared normal and were abundant in alveolar lumens. Tubular myelin was not seen, but is generally not observed in lung specimens routinely examined by electron microscopy (Reference [35] and personal observations, A.R.P-A.).…”

Section: Discussionmentioning

confidence: 59%

Pulmonary Pathology in Thyroid Transcription Factor-1 Deficiency Syndrome

Galambos

Levy

Cannon

et al. 2010

Am J Respir Crit Care Med

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Thyroid transcription factor-1 (TTF-1) deficiency syndrome is characterized by neurologic, thyroidal, and pulmonary dysfunction. Children usually have mild-to-severe respiratory symptoms and occasionally die of respiratory failure. Herein, we describe an infant with a constitutional 14q12-21.3 haploid deletion encompassing the TTF-1 gene locus who had cerebral dysgenesis, thyroidal dysfunction, and respiratory insufficiency. The clinical course was notable for mild hyaline membrane disease, continuous ventilatory support, and symmetrically distributed pulmonary cysts by imaging. He developed pneumonia and respiratory failure and died at 8 months. Pathologically, the lungs had grossly visible emphysematous changes with ''cysts'' up to 2 mm in diameter. The airway generations and radial alveolar count were diminished. In addition to acute bacterial pneumonia, there was focally alveolar septal fibrosis, pneumocyte hypertrophy, and clusters of airspace macrophages. Ultrastructurally, type II pneumocytes had numerous lamellar bodies, and alveolar spaces contained fragments of type II pneumocytes and extruded lamellar bodies. Although immunoreactivity for surfactant protein SP-A and ABCA3 was diminished, that for SP-B and proSP-C was robust, although irregularly distributed, corresponding to the distribution of type II pneumocytes. Immunoreactivity for TTF-1 protein was readily detected. In summation, we document abnormal airway and alveolar morphogenesis and altered expression of surfactant-associated proteins, which may explain the respiratory difficulties encountered in TTF-1 haploinsufficiency. These findings are consistent with experimental evidence documenting the important role of TTF-1 in pulmonary morphogenesis and surfactant metabolism.Keywords: alveolar growth abnormality; cerebral dysgenesis; thyroid transcription factor-1; bronchopulmonary dysplasia; surfactant protein Thyroid transcription factor-1 (TTF-1, also known as TITF-1, NKX2-1, or TEBP), a member of the NKx2 homeodomain transcription factor family, is essential for the morphogenesis of thyroid, lungs, and brain (3).TTF-1 knockout mice fail to develop these organs and die at birth, whereas the heterozygous mice reach term (4).TTF-1 haploinsufficiency in humans is responsible for a rare syndrome (TTF-1 deficiency syndrome) characterized by neurological, thyroidal, and pulmonary dysfunction (5-9). In a recent series that also reviewed the clinical and pathologic findings of 46 patients with TTF-1 deficiency, pulmonary disease occurred in 54%, with ''infant respiratory distress syndrome'' being the most common (7). The pulmonary pathology has been described briefly in one patient, whereas only one other case report illustrates the pathologic findings (10, 11).We identified an infant with cerebral dysgenesis, thyroidal dysfunction, respiratory insufficiency, and a karyotype showing a 14q13-21.3 deletion encompassing the TTF-1 gene locus. The infant died at 8 months with pneumonia and respiratory insufficiency. We describe his pulmonary pathology, incl...

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Section: Discussionmentioning

confidence: 59%

Pulmonary Pathology in Thyroid Transcription Factor-1 Deficiency Syndrome

Galambos

Levy

Cannon

et al. 2010

Am J Respir Crit Care Med

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“…One problem with surfactant overproduction is that sustained and uncontrolled over a period of time, it can become a pathological feature of silica exposure. Proteinosis and phospholipidosis of the lungs, secondary to silicosis, is characterized by appearance of tubular myelin-like multilamellated structures in the alveoli and distal airways [34].…”

Section: Modification Of Silica Toxicity By Lung Surfactantmentioning

confidence: 99%

Silica binding and toxicity in alveolar macrophages

Hamilton

Thakur

Holian

2008

Free Radical Biology and Medicine

335

242

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Inhalation of the crystalline form of silica is associated with a variety of pathologies from acute lung inflammation to silicosis, in addition to autoimmune disorders and cancer. Basic science researchers looking at the mechanisms involved with the earliest initiators of disease are focused on how the alveolar macrophage (AM) interacts with the inhaled silica particle and the consequences of silicainduced toxicity on the cellular level. Based on experimental results, several rationales have been developed on exactly how crystalline silica particles are toxic to the macrophage cell that is functionally responsible for clearance of the foreign particle. For example, silica is capable of producing reactive oxygen species (ROS) either directly (on the particle surface) or indirectly (produced by the cell as a response to silica) triggering cell-signaling pathways initiating cytokine release and apoptosis. With murine macrophages, reactive nitrogen species (RNS) are produced in the initial respiratory burst in addition to ROS. An alternative explanation for silica toxicity includes lysosomal permeability, where silica disrupts the normal internalization process leading to cytokine release and cell death. Still other research has focused on the cell surface receptors (collectively known as scavenger receptors) involved in silica binding and internalization. The silica-induced cytokine release and apoptosis is described as the function of receptor-mediated signaling rather than free radical damage. Current research ideas on silica toxicity and binding in the alveolar macrophage are reviewed and discussed.

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“…After secretion, alveolar forms of surfactant include these lamellar bodies, highly organised structures termed tubular myelin, and monolayered and multilayered, phospholipid-rich sheets and vesicles (Whitsett and Weaver, 2002). While the principal function of this pulmonary surfactant is the regulation of surface tension in the lungs (Nicholas, 1996), it is also postulated that increased production of this surfactant may play a role in defending the lungs against chemical and particulate damage (Hook, 1991(Hook, , 1993.…”

Section: Mtt Reduction (% Control)mentioning

confidence: 99%