Pulmonary dendritic cells in lungs of preterm infants: neglected participants in bronchopulmonary dysplasia?
Preterm infants are at risk for bronchopulmonary dysplasia (BPD), a chronic lung disease characterized by disrupted alveolar remodeling and microvascular dysangiogenesis. The pathogenesis of BPD is multifactorial, with contributions from antenatal and/or postnatal infection and inflammation. The potential role of dendritic cells, critical immune regulatory cells with potent angiogenic activities, remains undetermined. We studied the prevalence and topography of dendritic cells in postmortem lungs of short- and long-term ventilated preterm infants born between 23 and 29 weeks in gestation. Controls were age-matched infants who had lived less than 12 hours. Dendritic cells were identified by anti-DC-SIGN immunohistochemistry and were co-localized with endothelial and smooth muscle cells by double immunofluorescence. Lungs of early and late control infants without evidence of antenatal infection contained scattered DC-SIGN-positive dendritic cells in the peripheral lung parenchyma. Lungs of early control infants with a history of chorioamnionitis/antenatal infection and lungs of short- or long-term ventilated preterm infants showed a dramatic (more than 3-fold) increase in dendritic cells. Double labeling highlighted a close association between dendritic cells and small- or medium-sized pulmonary vessels. In conclusion, we demonstrated that dendritic cells are an integral component of normal postcanalicular lung development. Antenatal infection and ventilation/BPD are associated with significant pulmonary recruitment of dendritic cells. The recently described angiogenic effects of dendritic cells and their intimate association with the pulmonary microvasculature indicate that dendritic cells may participate in BPD-associated dysangiogenesis. Elucidation of the role of this immunovascular axis may lead to novel therapeutic approaches to BPD.
De Paepe
Monique E
ME
Department of Pathology, Women and Infants Hospital, Providence, RI, USA. mdepaepe@wihri.org
Hanley
L Corey
LC
Lacourse
Zacharie
Z
Pasquariello
Terese
T
Mao
Quanfu
Q
D001997:Bronchopulmonary Dysplasia / Q000276:immunology / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D007234:Infant, Premature / Q000276:immunology; D037181:Lectins, C-Type / Q000096:biosynthesis; D008168:Lung / Q000276:immunology / Q000473:pathology*; D008297:Male; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin