Tryptase immunoreactive mast cell hyperplasia in bronchopulmonary dysplasia
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R E Lyle1, A F Tryka, W S Griffin
1Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, USA.
Insights
Mast cells and tryptase are significantly increased in infants with bronchopulmonary dysplasia (BPD), a chronic lung disease. This suggests their potential role in the development of BPD fibrosis.
Area of Science:
- Pulmonary Pathology
- Immunohistochemistry
- Pediatric Lung Disease
Background:
- Bronchopulmonary dysplasia (BPD) is a leading cause of chronic lung disease in premature infants, characterized by airway and alveolar fibrosis.
- Tryptase, a mast cell-specific protease, promotes fibroblast growth and is elevated in adult fibrotic lung conditions.
- Mast cells and tryptase are implicated in fibrotic processes, warranting investigation in BPD.
Purpose of the Study:
- To investigate the distribution and quantity of tryptase-positive mast cells in infant lungs affected by BPD.
- To compare mast cell counts in BPD lungs with those in healthy controls.
Main Methods:
- Autopsy lung specimens from infants with BPD and SIDS (Sudden Infant Death Syndrome) controls were analyzed.
- Immunoperoxidase staining was used to identify tryptase-positive mast cells.
- Mast cell counts were quantified in bronchial, peribronchiolar, and alveolar regions at 250x magnification.
Main Results:
- Tryptase-positive mast cells were significantly increased in the bronchial and peribronchiolar regions of BPD lungs compared to controls.
- A dramatic increase in tryptase-positive mast cells was observed in alveolar regions with moderate to severe septal fibrosis in BPD.
- Counts in BPD bronchial regions were 23.9 +/- 3.6 vs. 14.4 +/- 2.3 in controls (P < 0.05).
- Counts in BPD alveolar regions with fibrosis were 9.83 +/- 1.89 vs. 0.34 +/- 0.18 in controls (P = 0.003).
Conclusions:
- There is a hyperplasia of tryptase-positive mast cells in infants with BPD.
- These findings suggest a potential role for mast cells and tryptase in the pathogenesis of BPD and its associated lung fibrosis.
Abstract:
Bronchopulmonary dysplasia (BPD), the most common cause of chronic lung disease in prematurely born infants, is histologically characterized by various degrees of airway and alveolar septal fibrosis. Tryptase, a serine protease specific to mast cells, has been shown to have potent fibroblast mitogenic properties and in addition has been shown to be increased in adult fibrotic lung disorders. Based on this analogy, the distribution of pulmonary mast cells exhibiting tryptase immunoreactivity was investigated by immunoperoxidase staining in autopsy specimens of infants dying with BPD. Morphologically normal lung specimens from similarly aged infants dying of sudden infant death syndrome (SIDS) served as controls. Tryptase-positive mast cell counts were performed at 250x from at least 10 random fields in bronchial, peribronchiolar, and alveolar regions. Compared to controls, in lung sections exhibiting typical histologic features of long-standing BPD, tryptase positive cells were significantly increased in bronchial (23.9 +/- 3.6 vs 14.4 +/- 2.3) and peribronchiolar (15.3 +/- 3.2 vs 4.63 +/- 0.6) regions compared to controls (P < 0.05, Student's t test). In particular, alveolar regions exhibiting moderate to severe degrees of septal fibrosis exhibited a dramatic increase in the number of tryptase-positive cells (9.83 +/- 1.89 vs 0.34 +/- 0.18, P = 0.003). These findings of a tryptase-positive mast cell hyperplasia in BPD suggest potential roles of mast cells as well as tryptase in the pathogenesis of this disease.