Disordered Pulmonary Myofibroblast Distribution and Elastin Expression in Preterm Infants with <i>Ureaplasma Urealyticum</i> Pneumonitis

Viscardi, Rose M.; Manimtim, Winston M; He, Ju; Hasday, Jeffrey D.; Sun, Chen‐Chih J.; Joyce, Belinda Jane; Pierce, Richard A.

doi:10.2350/10-05-0112.1

Cited by 44 publications

(34 citation statements)

References 38 publications

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“…Whether the early fibrosis noted at 2 wk of age persists or resolves over time in the antenatal UU-infected preterm baboon lung is unknown. In autopsy lung samples from human infants dying with Ureaplasma infection, myofibroblast accumulation and collagen and elastin deposition were evident up to 6 wk postnatal age (4,14). The observation that abnormalities persist despite clearance of the organism suggest that therapeutic interventions solely targeting organism eradication may be insufficient to prevent the infection-related sequelae.…”

Section: Discussionmentioning

confidence: 95%

“…TGF␤ was detected at sites of lung injury in association with myofibroblast proliferation in lungs of infants dying of respiratory distress syndrome, implicating TGF␤ in the preterm lung's response to injury (12). TGF␤ 1 is elevated in tracheal aspirates of infants who progress to BPD (13) and is increased in autopsy lung specimens from Ureaplasma-infected preterm infants (14). Overexpression of TGF␤ 1 in the newborn rodent lung produces a phenotype similar to human BPD with arrested lung sacculation, epithelial differentiation, and vascular development (15)(16)(17).…”

mentioning

confidence: 99%

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Antenatal Ureaplasma urealyticum Respiratory Tract Infection Stimulates Proinflammatory, Profibrotic Responses in the Preterm Baboon Lung

et al. 2006

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Section: Discussionmentioning

confidence: 95%

mentioning

confidence: 99%

Antenatal Ureaplasma urealyticum Respiratory Tract Infection Stimulates Proinflammatory, Profibrotic Responses in the Preterm Baboon Lung

et al. 2006

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“…Although lung morphometry was not performed on these animals, we did not observe changes on hematoxylin and eosin stains of unventilated ureaplasma infected controls. Human infants with ureaplasma pneumonitis develop increased pulmonary myofibroblast activation and disordered elastin formation (34). Baboons exposed to antenatal ureaplasma and then ventilated for 14 d have increased ␣-smooth muscle actin and fibrosis (35).…”

Section: Discussionmentioning

confidence: 99%

Ventilation-Mediated Injury After Preterm Delivery of Ureaplasma parvum Colonized Fetal Lambs

et al. 2010

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Ureaplasma species are the microorganisms most frequently isolated from women with preterm birth and are associated with an increased risk of bronchopulmonary dysplasia. Initiation of ventilation with high tidal volumes (V T ) causes lung injury and inflammation. We investigated whether antenatal colonization with Ureaplasma parvum serovar 3 (UP) would alter the inflammatory response to mechanical ventilation of preterm lambs. Merino ewes were given intraamniotic injections of UP at 55-d gestation, and the lambs were surgically delivered at 128 Ϯ 1 d gestation and assigned to three groups: 1) gentle ventilation (GV), 2) high V T ventilation, or 3) unventilated control. Lambs delivered from noncolonized ewes were assigned to parallel groups. GV lambs received surfactant before ventilation with a V T of 7 mL/kg, positive end expiratory pressure (PEEP) 5 cm H 2 O . High V T lambs received no PEEP and escalating V T to 15 mL/kg by 15 min. At 15 min, surfactant was given, V T was reduced to 7 mL/kg, and PEEP was increased to 5 cm H 2 O. Monocytes in bronchoalveolar lavage were increased by UP, but colonization did not affect lung function. High V T ventilation increased Egr-1 signaling, proinflammatory cytokine expression, and injury scores compared with GV. Antenatal colonization with UP did not change lung function or modulate the lung injury and inflammation caused by high V T ventilation. (Pediatr Res 67: 630-635, 2010)

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“…Instead of the normal location near the tips of the alveolar septa where alveolar wall formation is initiated, they appear randomly scattered around the alveolar wall. Alveolar myofibroblasts are interstitial contractile cells that are essential for secondary septation and that share many features of SMCs, including the production of elastin-rich extracellular matrix (5,12,43). Elastin expression is initiated early during the pseudoglandular stage of lung development, and, shortly after birth, elastin synthesis is upregulated with elastic fibers concentrating at the apex of developing secondary septal crests.…”

Section: Ajp-lung Cell Mol Physiolmentioning

confidence: 99%

Neuraminidase-1 is required for the normal assembly of elastic fibers

Starcher

d’Azzo²,

Keller³

et al. 2008

American Journal of Physiology-Lung Cellular and Molecular Phys

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The assembly of elastic fibers in tissues that undergo repeated cycles of extension and recoil, such as the lungs and blood vessels, is dependent on the proper interaction and alignment of tropoelastin with a microfibrillar scaffold. Here, we describe in vivo histopathological effects of neuraminidase-1 (Neu1) deficiency on elastin assembly in the lungs and aorta of mice. These mice exhibited a tight-skin phenotype very similar to the Tsk mouse. Normal septation of Neu1-null mice did not occur in neonatal mice, resulting in enlarged alveoli that were maintained in adults. The abnormal development of elastic fibers was remarkable under electron microscopy and confirmed by the overlapping distribution of elastin, fibrillin-1, fibrillin-2, and fibulin-5 (Fib-5) by the light microscopy immunostainings. Fib-5 fibers appeared diffuse and unorganized around the alveolar walls and the apex of developing secondary septal crests. Fibrillin-2 deposition was also abnormal in neonatal and adult lungs. Dispersion of myofibroblasts appeared abnormal in developing lungs of Neu1-null mice, with a random distribution of myofibroblast around the alveolar walls, rather than concentrating at sites of elastin synthesis. The elastic lamellae in the aorta of the Neu1-null mice were thinner and separated by hypertrophic smooth muscle cells that were surrounded by an excess of the sialic acid-containing moieties. The concentration of elastin, as measure by desmosine levels, was significantly reduced in the aorta of Neu1-null mice. Message levels for tropoelastin and Fib-5 were normal, suggesting the elastic fiber defects in Neu1-null mice result from impaired extracellular assembly. elastin; fibulin-5; fibrillin; extracellular matrix ELASTIN IS SYNTHESIZED in the cell as a soluble precursor, tropoelastin, which is transported to the cell surface bound to the 67-kDa elastin-binding protein, EBP, a recyclable molecular chaperone that facilitates the secretion of tropoelastin (6,31,32). EBP is an enzymatically inactive splice variant of lysosomal ␤-galactosidase (␤-Gal) and was originally named short ␤-Gal (S-Gal) (31). The orderly release of tropoelastin into the extracellular matrix occurs at the cell surface, where the tropoelastin is then assembled onto a scaffold of microfibrils and cross-linked by lysyl oxidase into mature elastic fibers. These elastic fibers are composed of two major components: a core containing resilient polymer elastin and 10-to 12-nm microfibrils made up of several structural glycoproteins; fibrillins (FBN) 1, 2, and 3, fibulins 1, 3, and 5 (Fib-5), and MAGP (8,

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Disordered Pulmonary Myofibroblast Distribution and Elastin Expression in Preterm Infants with Ureaplasma Urealyticum Pneumonitis

Cited by 44 publications

References 38 publications

Antenatal Ureaplasma urealyticum Respiratory Tract Infection Stimulates Proinflammatory, Profibrotic Responses in the Preterm Baboon Lung

Antenatal Ureaplasma urealyticum Respiratory Tract Infection Stimulates Proinflammatory, Profibrotic Responses in the Preterm Baboon Lung

Ventilation-Mediated Injury After Preterm Delivery of Ureaplasma parvum Colonized Fetal Lambs

Neuraminidase-1 is required for the normal assembly of elastic fibers

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