Disordered pulmonary myofibroblast distribution and elastin expression in preterm infants with Ureaplasma urealyticum pneumonitis.
Respiratory colonization of preterm infants with Ureaplasma urealyticum is a significant risk factor for bronchopulmonary dysplasia, a chronic lung disease characterized by arrest of alveolar development, variable interstitial fibrosis, and disordered elastic fibers in the distal airspaces. As indicated in previous studies, moderate to severe fibrosis is a hallmark of pathology in the Ureaplasma-infected preterm lung. To further characterize the preterm lung's response to Ureaplasma, lung specimens from 4 gestational controls (GC), 12 other pneumonia and 5 Ureaplasma-infected infants were analyzed by immunohistochemistry for alpha-smooth muscle actin (alphaSMA) and transforming growth factor beta1 (TGFbeta1), Hart's elastin staining, and in situ hybridization for tropoelastin (TE) expression. Cells positive for alphaSMA were observed in thickened, extensive bundles surrounding terminal airspaces in Ureaplasma and other pneumonia cases compared to individual myofibroblasts in GC. The myofibroblast pattern correlated with the severity of fibrosis, but not duration of ventilation. Transforming growth factor beta1 immunostaining was primarily localized to alveolar macrophages and was increased in Ureaplasma more than in other pneumonia cases. Elastic fibers and TE-expressing cells were spatially limited to emerging septal tips in GC. In pneumonia cases, increased deposition of elastic fibers was observed surrounding terminal airspaces, but TE expression was similar to GC. In Ureaplasma specimens, accumulation of elastic fibers correlated with duration of ventilation, and TE expression was extensive throughout the walls of terminal airspaces. These findings suggest that Ureaplasma is associated with alveolar macrophage TGFbeta1 immunostaining and myofibroblast proliferation contributing to abnormal septation, interstitial fibrosis, and a prolonged and strong elastogenic response in the preterm lung.
Viscardi
Rose
R
Department of Pediatrics, University of Maryland School of Medicine, 22 South Greene Street, Baltimore, 21201, USA. rviscard@umaryland.edu
Manimtim
Winston
W
He
Ju Ren
JR
Hasday
Jeffrey D
JD
Sun
Chen-Chih J
CC
Joyce
Belinda
B
Pierce
Richard A
RA
D000199:Actins / Q000378:metabolism; D004549:Elastin / Q000378:metabolism*; D005347:Fibroblasts / Q000473:pathology*; D006801:Humans; D017403:In Situ Hybridization; D007231:Infant, Newborn; D007234:Infant, Premature; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D018410:Pneumonia, Bacterial / Q000378:metabolism / Q000473:pathology*; D011658:Pulmonary Fibrosis / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D014333:Tropoelastin / Q000235:genetics / Q000378:metabolism; D016869:Ureaplasma Infections / Q000378:metabolism / Q000473:pathology*; D016990:Ureaplasma urealyticum / Q000302:isolation & purification*
D000199:Actins; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014333:Tropoelastin; D004549:Elastin