High expression of pulmonary proteinase-activated receptor 2 in acute and chronic lung injury in preterm infants.
Proteinase-activated receptor 2 (PAR(2)), a G-protein-coupled receptor activated by serine proteinases such as trypsin, has been suggested to play an important role in inflammatory and fibroproliferative processes. In preterm infants, the development of bronchopulmonary dysplasia (BPD) is characterized by early pulmonary inflammation and subsequent interstitial fibrosis. High pulmonary trypsin-2 has been shown to be associated with the development of BPD. We studied the expression and distribution of PAR(2) and trypsin-2 by immunohistochemistry in autopsy lung specimens of fetuses (n = 10), of preterm infants who died of acute or prolonged respiratory distress syndrome (RDS) (n = 8 and n = 7, respectively) or BPD (n = 6), and of newborn infants without lung disease (n = 5) who served as controls. In prolonged RDS and BPD, PAR(2) immunoreactivity was significantly higher in bronchial epithelium when compared with infants without pulmonary pathology (p < 0.05 and p < 0.005, respectively). In alveolar epithelium, expression of PAR(2) was elevated in prolonged RDS when compared with newborn infants without pulmonary pathology (p < 0.05). Moreover, strong expression of PAR(2) was detected in myofibroblasts of thickened and fibrotic alveolar walls in prolonged RDS or BPD. Trypsin-2 was co-localized with PAR(2) in bronchoalveolar epithelium. These findings suggest that PAR(2), possibly activated by trypsin-2, may participate in inflammation and fibroproliferation associated with progression of RDS toward BPD in preterm infants.
Cederqvist
Katariina
K
Hospital for Children and Adolescents, University of Helsinki, FIN-00029 Helsinki, Finland. katariina.cederqvist@helsinki.fi
Haglund
Caj
C
Heikkilä
Päivi
P
Hollenberg
Morley D
MD
Karikoski
Riitta
R
Andersson
Sture
S
D000208:Acute Disease; D001997:Bronchopulmonary Dysplasia / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D002908:Chronic Disease; D005333:Fetus / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D007234:Infant, Premature; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000473:pathology; D044464:Receptor, PAR-2 / Q000378:metabolism*; D012127:Respiratory Distress Syndrome, Newborn / Q000378:metabolism* / Q000473:pathology; D014357:Trypsin / Q000378:metabolism; D014362:Trypsinogen / Q000378:metabolism
D044464:Receptor, PAR-2; C064831:PRSS2 protein, human; D014362:Trypsinogen; D014357:Trypsin