Development of Alveolar Septa and Formation of Alveolar Pores during the Early Postnatal Period in the Rat Lung

Scheuermann, D.W.; Meir, F. van; Adriaensen, Dirk; Timmermans, Jean‐Pierre; Groodt-Lasseel, M.H.A. de

doi:10.1159/000146524

Cited by 15 publications

(11 citation statements)

References 8 publications

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“…In the rat, other organs, such as the intestines, lungs, and liver, undergo postnatal development (2,26,28,43), express AT 1 receptors (29, 31, 36), and upregulate MHC II (22). However, the present study shows that MHC II expression in other postnatally developing organs is unaffected by AT 1 -receptor inhibition, pointing to a specific association between the RAS and MHC II in the developing TALH.…”

Section: Discussioncontrasting

confidence: 60%

“…The primary aims of the present study were to examine 1) the temporal and spatial changes in renal MHC II expression after neonatal losartan treatment; 2) whether the losartan effect is direct or may be related to hemodynamic changes, by comparing losartan with nifedipine (a calcium channel blocker); and 3) whether the losartan effect on MHC II expression is specific to the developing kidney. Although other organs, such as intestines, lungs, and liver, undergo postnatal development (2,26,28,43), express AT 1 receptors (29,31,36), and upregulate MHC II (22), only in the kidney are irreversible developmental defects found after interrupted neonatal AT 1 receptor signaling (8). Our data have shown that losartan abolished MHC II expression exclusively in epithelial cells of the developing thick ascending limb of Henle (TALH), raising the hypothesis of specific changes in the TALH phenotype after neonatal RAS inhibition.…”

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confidence: 74%

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Neonatal RAS inhibition changes the phenotype of the developing thick ascending limb of Henle

Lasaitiene¹,

Friberg²,

Sundelin³

et al. 2004

American Journal of Physiology-Renal Physiology

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Pharmacological interruption of angiotensin II type 1 (AT(1)) receptor signaling during nephrogenesis in rats perturbs renal tubular development. Perturbed tubulogenesis may contribute to long-term impairment of urinary concentrating ability, which is the main functional irreversible defect. The aim of this study was to further characterize tubular developmental deficits in neonatal rats, focusing on the thick ascending limb of Henle (TALH), known to undergo profound developmental changes and to be involved in urine-concentrating mechanisms. We have carried out immunohistochemistry and Western immunoblotting using antibodies directed against the major histocompatibility complex class II (MHC II) molecule and different TALH-specific markers, namely, cyclooxygenase-2 (COX-2), Tamm-Horsfall glycoprotein (THP), and the bumetanide-sensitive Na(+)-K(+)-2Cl(-) cotransporter (BSC-1/NKCC2). Immunohistochemistry demonstrated expression of MHC II, COX-2, THP, and BSC-1/NKCC2 proteins in normally developing TALH cells. The AT(1)-receptor antagonist losartan abolished MHC II expression exclusively in the developing TALH cells. Increased expression of COX-2 and THP was observed in the TALH cells of losartan-treated rats. Western immunoblotting confirmed increases in cortical and medullary COX-2 and THP abundance and revealed a decrease in cortical BSC-1/NKCC2 abundance in response to losartan treatment. We conclude that neonatal losartan treatment causes significant changes in the phenotype of the developing TALH in the rat.

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Section: Discussioncontrasting

confidence: 60%

mentioning

confidence: 74%

Neonatal RAS inhibition changes the phenotype of the developing thick ascending limb of Henle

Lasaitiene¹,

Friberg²,

Sundelin³

et al. 2004

American Journal of Physiology-Renal Physiology

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“…Secondary crests were identified as partitions that extended from the primary septa forming the walls of terminal sacs. Initial low secondary crests were observed as early as P1, as was reported previously (18). Numbers of alveolar secondary crests per HPF were counted for four to eight HPF images per lung and two to three lungs per group at each time point.…”

Section: Methodsmentioning

confidence: 72%

Altered Expressions of Fibroblast Growth Factor Receptors and Alveolarization in Neonatal Mice Exposed to 85% Oxygen

Park

Rieger‐Fackeldey

Schanbacher³

et al. 2007

Pediatr Res

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ABSTRACT:In the present study, we tested the hypothesis that exposure of newborn mice to sublethal hyperoxia would alter lung development and expressions of fibroblast growth factor receptors (FGFRs)-3 and FGFR-4. Newborn FVB mice were exposed to 85% O 2 or maintained in room air for up to 14 d. No animal mortality was observed, and body weight gains were not affected by hyperoxia. At postnatal d 7 and 14 (P7, P14), lungs of mice exposed to 85% O 2 showed fewer alveolar secondary crests and larger alveoli or terminal air spaces than did mice in room air. In pups kept in room air, lung levels of FGFR-3 and FGFR-4 mRNA were greater at P3 than at P1, but similar increases were not observed in hyperoxic mice. Immunoreactivity of FGFR-3 and FGFR-4 was lower in lungs of hyperoxic mice than in controls at P14. In pups kept in room air, lung fibroblast growth factor (FGF)-7 mRNA levels were greater at P14 than at P1, but similar changes were not observed in hyperoxic mice. The temporally and spatially specific alterations in the expressions of FGFR-3, FGFR-4, and FGF-7 in the mice exposed to hyperoxia may contribute to aberrant lung development. B ronchopulmonary dysplasia (BPD) was described initially as lung injury-and repair-related effects that were associated with radiologic findings of streaky, fibrous densities, alternating with hyperlucent areas (1,2). The primary risk factors were premature birth, respiratory distress, mechanical ventilation, and administration of supplemental oxygen (FIO 2 Ͼ0.21). Inflammation, problems in nutritional support, and comorbid conditions also contribute to the development of BPD. Modifications of therapeutic strategies have decreased the incidence of BPD, as the disease was described originally, but the overall incidence of BPD has not declined. The "new BPD" of recent years shows little acute injury and repair described by Northway et al. (1,2), but is characterized by fewer and larger alveoli and less organized alveolar vascularization, suggesting arrested or disordered lung development. The events occurring during secondary septation of terminal gas exchange units and maturation of alveolar microvasculature are therefore of particular interest in research on mechanisms responsible for the new BPD (3-8).Lung development in humans normally progresses through sequential structural changes that are observed similarly in rats and mice, which, at term, exhibit lungs that structurally resemble human lungs at 26 -30 wk of gestation (9). Infants born at this age frequently encounter respiratory problems, arising from immature pulmonary surfactant metabolism, respiratory drive and coordination, or other deficiencies. Prematurely delivered nonhuman primate models of BPD may mimic human development more closely than do rodent models, but practical constraints limit the investigations that can be explored with primate models (4,5,10).The lungs of newborn rodents are sufficient for extrauterine life and are adequate for maturation into normal adult lungs. Studies in rats and mice indicate th...

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“…Also, submucosal glands are present in both ovine and human lungs, but not in rodents, and these produce lactoperoxidase, which is essential for the epithelial oxidative defense system. Unlike rodents, alveolar development occurs preterm in both humans and lambs (5,22,33). Lambs are susceptible to infection by both ovine and bovine strains of RSV, and can be experimentally infected with the human RSV A2 strain (hRSV).…”

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confidence: 99%

Respiratory syncytial virus is associated with an inflammatory response in lungs and architectural remodeling of lung-draining lymph nodes of newborn lambs

Sow

Gallup

Olivier

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

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is the leading cause of lower respiratory tract infection in children worldwide. The understanding of neonatal RSV pathogenesis depends on using an animal model that reproduces neonatal RSV disease. Previous studies from us and others demonstrated that the neonatal lamb model resembles human neonatal RSV infection. Here, we provide an extensive and detailed characterization of the histopathology, viral load, cellular infiltration, and cytokine production in lungs and tracheobronchial lymph nodes of lambs inoculated with human RSV strain A2 over the course of infection. In the lung, RSV titers were low at day 3 postinfection, increased significantly by day 6, and decreased to baseline levels at day 14. Infection in the lung was associated with an accumulation of macrophages, CD4 ϩ and CD8 ϩ T cells, and a transcriptional response of genes involved in inflammation, chemotaxis, and interferon response, characterized by increased IFN␥, IL-8, MCP-1, and PD-L1, and decreased IFN␤, IL-10, and TGF-␤. Laser capture microdissection studies determined that lung macrophage-enriched populations were the source of MCP-1 but not IL-8. Immunoreactivity to caspase 3 occurred within bronchioles and alveoli of day 6-infected lambs. In lung-draining lymph nodes, RSV induced lymphoid hyperplasia, suggesting an ability of RSV to enhance lymphocytic proliferation and differentiation pathways. This study suggests that, in lambs with moderate clinical disease, RSV enhances the activation of caspase cell death and Th1-skewed inflammatory pathways, and complements previous observations that emphasize the role of inflammation in the pathogenesis of RSV disease. lung; neonate; immune response; sheep HUMAN RESPIRATORY SYNCYTIAL VIRUS (RSV) is the leading cause of severe lower respiratory tract illnesses in premature/newborn infants and young children. The World Health Organization (WHO) estimates that in the United States alone, 70,000 to 126,000 infant hospitalizations for pneumonia or bronchiolitis are attributed to RSV every year (43). Furthermore, global annual RSV infections are estimated by the WHO at 64 million, with 160,000 deaths occurring yearly. Immunocompromised individuals (30) and the elderly (14) are also at risk for severe RSV disease, whose manifestations include rhinitis, bronchitis, otitis media, and pneumonia (31). Despite the importance of RSV as a pathogen, there is no currently licensed vaccine for RSV. Challenges encountered for the successful development of a pediatric RSV vaccine include the relatively immature immune response of infants, the potential interference of maternal antibodies with vaccinations, and previous concerns of vaccine-induced enhanced disease severity (reviewed in Ref. 40). However, some progress has been made with prophylaxis using the humanized anti-RSV monoclonal antibody palivizumab (20). Palivizumab is indicated for the prevention of serious lower respiratory tract disease caused by RSV in high-risk children (premature infants and children less than 2 years of age with chronic lung disease ...

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Development of Alveolar Septa and Formation of Alveolar Pores during the Early Postnatal Period in the Rat Lung

Cited by 15 publications

References 8 publications

Neonatal RAS inhibition changes the phenotype of the developing thick ascending limb of Henle

Neonatal RAS inhibition changes the phenotype of the developing thick ascending limb of Henle

Altered Expressions of Fibroblast Growth Factor Receptors and Alveolarization in Neonatal Mice Exposed to 85% Oxygen

Respiratory syncytial virus is associated with an inflammatory response in lungs and architectural remodeling of lung-draining lymph nodes of newborn lambs

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