Distribution of surfactant proteins in type II pneumocytes of newborn, 14-day old, and adult rats: an immunoelectron microscopic and stereological study

Schmiedl, Andreas; Ochs, Matthias; Mühlfeld, Christian; Johnen, Georg; Brasch, Frank

doi:10.1007/s00418-005-0066-0

Cited by 43 publications

(36 citation statements)

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“…Immunohistochemistry of lung tissue (25,42) and of isolated cells by light microscopy (24, 41) has demonstrated SP-A in type II cells, but the lamellar bodies generally appear as empty vesicles that fail to label with anti-SP-A antibody. Studies at the electron-microscopic level using immunogold techniques have produced similar results: goldlabeled anti-SP-A antibody could be localized to the lamellar body membrane, but with few exceptions, very little gold labeling was observed within the lamellar body contents (12,27,33,34,38). It has been recognized that this relatively poor detection of SP-A may be due to various technical issues (17,38).…”

Section: Discussionmentioning

confidence: 78%

Pathway to lamellar bodies for surfactant protein A

Fisher

Dodia

Rückert

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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surfactant protein A (SP-A) is endocytosed by type II epithelial cells through clathrindependent uptake and targeted to lamellar bodies for resecretion. However, the mechanism for secretion of newly synthesized SP-A, whether regulated exocytosis of lamellar bodies or constitutive secretion, is unresolved. If it is the latter, lamellar body SP-A would represent endocytosed protein. Amantadine, an inhibitor of clathrincoated vesicle budding, was used to evaluate the role of endocytosis in accumulation of SP-A in lamellar bodies. In isolated rat lungs, amantadine (10 mM) inhibited uptake of endotracheally instilled 35 S-labeled biosynthesized surfactant proteins by Ͼ80%. To study trafficking of newly synthesized SP-A, lungs were perfused for up to 6 h with [35 S]methionine, and surfactant was isolated from lung lavage fluid and lamellar bodies were isolated from lung homogenate. With control lungs, the mean specific activity of [ 35 S]SP-A (disintegrations per minute per microgram of SP-A) increased linearly with time of perfusion: it was significantly higher in isolated lamellar bodies than in surfactant and was increased in both compartments by 50 -60% in the presence of 0.1 mM 8-bromo-cAMP. These results suggest a precursor-product relationship between lamellar body and extracellular [35 S]SP-A. Specific activities in both compartments were unaffected by addition of amantadine (10 mM) to the lung perfusate, indicating that uptake from the alveolar space was not responsible for the increase in lamellar body [35 S]SP-A. Thus the pathway for secretion of newly synthesized SP-A is by transfer from the site of synthesis to the storage/secretory organelle prior to lamellar body exocytosis. protein trafficking; surfactant secretion; alveolar epithelial type II cell; protein synthesis; clathrin-dependent endocytosis THERE IS GENERAL AGREEMENT that lung surfactant phospholipids and surfactant proteins B and C (SP-B and SP-C) are synthesized in the endoplasmic reticulum of lung alveolar type II epithelial cells and transported to the lamellar bodies for processing and storage prior to secretion into the alveolar space. However, there is less agreement concerning the intracellular trafficking of SP-A. Like SP-B and SP-C, SP-A is synthesized by type II cells and is secreted into the alveolar space, where it associates with the lung surfactant phospholipids (19,22,37). Extracellular SP-A appears to play crucial roles in the formation of tubular myelin, in the regulation of lamellar body exocytosis, and in the uptake of phospholipids by endocytosis and their subsequent remodeling (20,23,30,40). The uptake process is dependent on the association of phospholipids with SP-A, followed by binding of the SP-Aphospholipid complex to a specific cell membrane-localized SP-A receptor (4,5,16), and then internalization of the complex by a clathrin-dependent pathway (21,32,35). Although the pathway for uptake of SP-A seems to be fairly well understood, there is uncertainty regarding the pathway for secretion of newly synthesized SP-A by ...

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Section: Discussionmentioning

confidence: 78%

Pathway to lamellar bodies for surfactant protein A

Fisher

Dodia

Rückert

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…On the other hand, after segmental allergen challenge in patients with asthma the BALF contained increased SP-D but decreased SP-A values [24]. Decreased SP-A levels have also been found in BALF of asthma patients [42], in asthmatic BN rats after OVA sensitization and challenge by inhalation of an aerosol of 5% OVA [43] and in the BALF of sensitized BALB/c mice after allergen challenge [20, 44]. An increase of SP-D was consistently described in animal models [21, 22, 25, 44].…”

Section: Discussionmentioning

confidence: 99%

Increased Surfactant Protein A and D Expression in Acute Ovalbumin-Induced Allergic Airway Inflammation in Brown Norway Rats

Schmiedl

Lührmann

Pabst

et al. 2008

Int Arch Allergy Immunol

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Background: The surfactant proteins SP-A and SP-D, components of the innate immune system, are involved in host defence. Objective: We tested the hypothesis that ovalbumin (OVA) challenge leads to an upregulation of both proteins in alveolar epithelial type II cells (AEII) and Clara cells and to an enhanced uptake by macrophages. Methods: After sensitization with OVA and heat-killed Bordetella pertussis challenge followed intratracheally with 0.5% OVA on day 13. One day after challenge lung tissue and bronchoalveolar lavage fluid (BALF) of sensitized NaCl- and OVA-challenged Brown Norway rats were compared with home cage controls using qRt-PCR, Western blot and immunohistochemistry. Results: After OVA challenge (1) eosinophils increased significantly in the BALF, (2) the total amount of SP-A and SP-D was significantly increased in lung tissue, (3) the amount of SP-A was significantly and the amount of SP-D was remarkably elevated in BALF, and (4) the levels of SP-A and SP-D mRNA in lung tissue were significantly elevated. Using quantitative immunohistochemistry, we found (5) significantly higher surface fractions of SP-A- and SP-D-labelled AEII, (6) no differences in the surface fractions of SP-A- and SP-D-labelled bronchial Clara cells, and (7) a significantly increased cell density of unlabelled and SP-A-labelled macrophages. Conclusions: Thus, combining molecular biological and histological methods we suggest that after OVA challenge (1) AEII but not Clara cells show a significantly higher expression of SP-A and SP-D leading also to higher amounts of both SPs in BALF and (2) macrophages gather predominantly SP-A.

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“…It is important to note, however, that the ability for rats to be born at term with anatomically immature lungs is largely due to the production of surfactant at birth. In contrast to human lungs, it has been shown that all four surfactant proteins (SP-A, -B, -C, and -D) can be detected in the type II pneumocytes in newborn rat lungs (49). In humans, the pulmonary surfactant system matures between 29 and 32 wk of gestation, which coincides with the saccular stage of lung development (52).…”

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confidence: 99%

Animal models of bronchopulmonary dysplasia. The term rat models

O’Reilly

Thébaud

2014

American Journal of Physiology-Lung Cellular and Molecular Phys

181

149

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O'Reilly M, Thébaud B. Animal models of bronchopulmonary dysplasia. The term rat models. Am J Physiol Lung Cell Mol Physiol 307: L948 -L958, 2014. First published October 10, 2014; doi:10.1152/ajplung.00160.2014.-Bronchopulmonary dysplasia (BPD) is the chronic lung disease of prematurity that affects very preterm infants. Although advances in perinatal care have enabled the survival of infants born as early as 23-24 wk of gestation, the challenge of promoting lung growth while protecting the ever more immature lung from injury is now bigger. Consequently, BPD remains one of the most common complications of extreme prematurity and still lacks specific treatments. Progress in our understanding of BPD and the potential of developing therapeutic strategies have arisen from large (baboons, sheep, and pigs) and small (rabbits, rats, and mice) animal models. This review focuses specifically on the use of the rat to model BPD and summarizes how the model is used in various research studies and the advantages and limitations of this particular model, and it highlights recent therapeutic advances in BPD by using this rat model. hyperoxia; lung development; premature birth BRONCHOPULMONARY DYSPLASIA (BPD) is the most common chronic lung disease of very preterm infants. BPD interrupts lung development and has serious long-term respiratory complications that reach beyond childhood and into adult life (8,25,26,41,53). The multifactorial etiology of BPD has prompted research to investigate the many factors contributing to the pathogenesis of BPD (reviewed in Ref. 38), with the ultimate aim of developing effective therapies to prevent longterm pulmonary sequelae. To investigate the effectiveness of various therapeutic strategies on the development, structure, and function of the lungs, it is important to have animal models that reliably reproduce some of the features observed in very preterm infants developing BPD. To achieve this, known contributing factors of BPD, such as perinatal inflammation, growth restriction, hyperoxia, and mechanical ventilation, have been used in both large and small animals to mimic the BPD-like lung injury. In particular, exposure of neonatal rats to hyperoxia is extensively utilized as a small animal model of experimental BPD. Characterization of the Rat Model of Experimental BPDExposing the immature rat lung to hyperoxic gas through neonatal life closely reproduces the histopathology observed in human infants with BPD. Studies have shown that exposure of the developing rat lung to hyperoxic gas can have detrimental effects, particularly on the structure of the gas-exchanging region (14,30,34,46,62,66). The main overall finding, which is common to each study, is that exposure of the immature lung to hyperoxic gas impairs alveolarization, resulting in fewer and enlarged alveolar air spaces. Pulmonary hypertension, disrupted vascular growth, vascular leakage, accumulation of plasma proteins, extravascular fibrin deposition, increased lung collagen content, increased inflammatory cell influx, and diso...

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Distribution of surfactant proteins in type II pneumocytes of newborn, 14-day old, and adult rats: an immunoelectron microscopic and stereological study

Cited by 43 publications

References 50 publications

Pathway to lamellar bodies for surfactant protein A

Pathway to lamellar bodies for surfactant protein A

Increased Surfactant Protein A and D Expression in Acute Ovalbumin-Induced Allergic Airway Inflammation in Brown Norway Rats

Animal models of bronchopulmonary dysplasia. The term rat models

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