"We speculate that such a BPD phenotype may be secondary to enhanced M1 macrophage recruitment in lungs upon IFNγ stimulation. The importance of classically activated M1 macrophages in the pathogenesis of lung injury is also supported by several other reports that suggest that direct activation of these cells can augment tissue damage [34, 36, 37]. "
[Show abstract][Hide abstract] ABSTRACT: Rationale. Hyperoxia exposure to developing lungs-critical in the pathogenesis of bronchopulmonary dysplasia-may augment lung inflammation by inhibiting anti-inflammatory mediators in alveolar macrophages. Objective. We sought to determine the O2-induced effects on the polarization of macrophages and the role of anti-inflammatory BRP-39 in macrophage phenotype and neonatal lung injury. Methods. We used RAW264.7, peritoneal, and bone marrow derived macrophages for polarization (M1/M2) studies. For in vivo studies, wild-type (WT) and BRP-39(-/-) mice received continuous exposure to 21% O2 (control mice) or 100% O2 from postnatal (PN) 1 to PN7 days, along with intranasal lipopolysaccharide (LPS) administered on alternate days (PN2, -4, and -6). Lung histology, bronchoalveolar lavage (BAL) cell counts, BAL protein, and cytokines measurements were performed. Measurements and Main Results. Hyperoxia differentially contributed to macrophage polarization by enhancing LPS induced M1 and inhibiting interleukin-4 induced M2 phenotype. BRP-39 absence led to further enhancement of the hyperoxia and LPS induced M1 phenotype. In addition, BRP-39(-/-) mice were significantly more sensitive to LPS plus hyperoxia induced lung injury and mortality compared to WT mice. Conclusions. These findings collectively indicate that BRP-39 is involved in repressing the M1 proinflammatory phenotype in hyperoxia, thereby deactivating inflammatory responses in macrophages and preventing neonatal lung injury.
Mediators of Inflammation 11/2013; 2013(7):457189. DOI:10.1155/2013/457189 · 3.24 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Bronchopulmonary dysplasia (BPD) remains an important complication of preterm births. The soluble form of ST2 (sST2), interleukin-33 (IL-33), and soluble form of the urokinase plasminogen activator receptor (suPAR) have attracted increasing attention as biomarkers for different diseases. The aim of the current study was to assess the predictive value of plasma sST2, IL-33, and suPAR levels in patients with risk of BPD development.
A total of 38 babies were studied prospectively on delivery to the neonatal intensive care unit. Serum levels of IL-33, sST2, and suPAR were measured using enzyme-linked immunosorbent assay. Serum samples were collected from umbilical cord (at the time of delivery, termed CB) and peripheral blood (on day 14, termed PB).
Levels of suPAR (PB-suPAR) and sST2 (PB-sST2) in the peripheral blood of the BPD group were significantly higher than the corresponding levels in the non-BPD group (P < 0.001, P = 0.028, respectively. There was a statistically significant correlation between PB-suPAR levels and the severity of BPD (P < 0.001)) when the suPAR results were analyzed using the receiver operating characteristic curve.
PB-suPAR and PB-sST2 levels are sensitive and specific independent predictive biomarkers in preterm babies with BPD.
Pediatric Research 03/2014; 75(6). DOI:10.1038/pr.2014.28 · 2.31 Impact Factor
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