Tryptase immunoreactive mast cell hyperplasia in bronchopulmonary dysplasia

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.

Genome-Wide Transcriptional Profiling Reveals Connective Tissue Mast Cell Accumulation in Bronchopulmonary Dysplasia

“…We validated the mast cell-specific gene expression patterns by qPCR and by demonstrating an approximately fivefold increase in the total number of mast cells in BPD tissues, as defined by IHC for tryptase. Increased mast cell accumulation has been previously identified as a feature of BPD (39) and has been observed in some animal models of disease (8,40), but the significance of these prior observations is not clear. Subramaniam and colleagues identified a role for increased expression of bombesin-like peptides (BLP) in a baboon model of BPD (8).…”

Imbalance between Cysteine Proteases and Inhibitors in a Baboon Model of Bronchopulmonary Dysplasia

“…Instead, cat K was detected in mast cells in 125-and 140-d lung tissues by immunohistochemistry (S.C., unpublished data) and in some interstitial cells in perivascular locations, also likely mast cells, in BPD by in situ hybridization. Mast cell hyperplasia is a well-known feature of BPD (37,38) and, taken together with our findings, this phenomenon can explain the source of increased cat K levels in BPD. Although cat K expression was previously reported in human bronchial and alveolar epithelial cells in one study (39), we could not confirm these findings in baboon lung tissues.…”

SERPINB1 upregulation is associated with in vivo complex formation with neutrophil elastase and cathepsin G in a baboon model of bronchopulmonary dysplasia

“…All of these cell types are involved in the inflammatory response that is observed in human infants with BPD (23,45). In the baboon model of new BPD, a dominance of macrophages was observed on differential cell counts of BALF obtained on day 14 (1), whereas in the old BPD model, neutrophils were predominant although macrophage numbers were also elevated (10).…”