Surfactant Proteins A and D in Premature Baboons with Chronic Lung Injury (Bronchopulmonary Dysplasia)

Awasthi, Shanjana; Coalson, Jacqueline J.; Crouch, Erika C.; Yang, Funmai; King, Richard J.

doi:10.1164/ajrccm.160.3.9806061

Cited by 67 publications

(64 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, increased mRNA did not always correlate with increased protein in lavage (54). Increased mRNA for Sftpa, Sftpb, Sftpc, and Sftpd is seen in newborn rats exposed to 85% oxygen (55).…”

Section: Discussionmentioning

confidence: 81%

Neonatal Hyperoxia Stimulates the Expansion of Alveolar Epithelial Type II Cells

Yee¹,

Buczynski

O’Reilly³

2014

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

Supplemental oxygen used to treat infants born prematurely disrupts angiogenesis and is a risk factor for persistent pulmonary disease later in life. Although it is unclear how neonatal oxygen affects development of the respiratory epithelium, alveolar simplification and depletion of type II cells has been observed in adult mice exposed to hyperoxia between postnatal Days 0 and 4. Because hyperoxia inhibits cell proliferation, we hypothesized that it depleted the adult lung of type II cells by inhibiting their proliferation at birth. Newborn mice were exposed to room air (RA) or hyperoxia, and the oxygenexposed mice were recovered in RA. Hyperoxia stimulated mRNA expressed by type II (Sftpc, Abca3) and type I (T1a, Aquaporin 5) cells and inhibited Pecam expressed by endothelial cells. 5-Bromo-2'-deoxyuridine labeling and fate mapping with enhanced green fluorescence protein controlled statically by the Sftpc promoter or conditionally by the Scgb1a1 promoter revealed increased Sftpc and Abca3 mRNA seen on Day 4 reflected an increase in expansion of type II cells shortly after birth. When mice were returned to RA, this expanded population of type II cells was slowly depleted until few were detected by 8 weeks. These findings reveal that hyperoxia stimulates alveolar epithelial cell expansion when it disrupts angiogenesis. The loss of type II cells during recovery in RA may contribute to persistent pulmonary diseases such as those reported in children born preterm who were exposed to supplemental oxygen.

show abstract

Section: Discussionmentioning

confidence: 81%

Neonatal Hyperoxia Stimulates the Expansion of Alveolar Epithelial Type II Cells

Yee¹,

Buczynski

O’Reilly³

2014

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

show abstract

“…The SP-A content of BALF has been shown to vary in individuals with various lung diseases (3)(4)(5). Moreover, qualitative and quantitative differences have been observed in vitro between the SP-A1 and SP-A2 genes (22,36,57,60,(77)(78)(79)(80)(81), pointing to the possibility that the overall functional activity of SP-A may depend on the relative SP-A1-to-SP-A2 levels rather than on the total SP-A content.…”

Section: Discussionmentioning

confidence: 99%

“…More than 30 alleles have been characterized for these two genes, with four SP-A1 alleles (6A, 6A 2 , 6A 3 , and 6A 4 ) and six SP-A2 alleles (1A, 1A 0 , 1A 1 , 1A 2 , 1A 3 , and 1A 5 ) most frequently observed in the general population (10,14,16,40,67). Although a high level of sequence similarity is shared among the SP-A genes and their corresponding alleles, in vitro studies have identified both qualitative (22,36,57,60,77,80,81) and quantitative (24,35,38,46,56,69,70,78,79) differences between the two genes.…”

mentioning

confidence: 99%

“…Significantly higher levels of SP-A have been reported in alveolar proteinosis (AP) (34,47,72), sarcoidosis, and hypersensitivity pneumonitis patients (32). Decreased SP-A levels were observed in inflammatory lung diseases (68), patients with bacterial pneumonia (5), bronchopulmonary dysplasia infection in baboons (3), and interstitial pneumonia with collagen vascular disease (47). For idiopathic pulmonary fibrosis (IPF), both decreased (55) and increased levels (33,48,64) of SP-A have been reported.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Characterization of a human surfactant protein A1 (SP-A1) gene-specific antibody; SP-A1 content variation among individuals of varying age and pulmonary health

Tagaram¹,

Wang²,

Umstead³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

The human surfactant protein A (SP-A) locus consists of two functional genes (SP-A1, SP-A2) with gene-specific products exhibiting qualitative and quantitative differences. The aim here was twofold: 1) generate SP-A1 genespecific antibody, and 2) use this to assess gene-specific SP-A content in the bronchoalveolar lavage fluid (BALF). An SP-A1-specific polyclonal antibody (hSP-A1_Ab 68-88 _Col) was raised in chicken, and its specificity was determined by immunoblot and ELISA using mammalian Chinese hamster ovary (CHO) cell-expressed SP-A1 and SP-A2 variants and by immunofluorescence with stably transfected CHO cell lines expressing SP-A1 or SP-A2 variants. SP-A1 content was evaluated according to age and lung status. A gradual decrease (P Ͻ 0.05) in SP-A1/SP-A ratio was observed in healthy subjects (HS) with increased age, although no significant change was observed in total SP-A content among age groups. Total SP-A and SP-A1 content differed significantly between alveolar proteinosis (AP) patients and HS, with no significant difference observed in SP-A1/SP-A ratio between AP and HS. The cystic fibrosis (CF) ratio was significantly higher compared with AP, HS, and noncystic fibrosis (NCF), even though SP-A1 and total SP-A were decreased in CF compared with most of the other groups. The ratio was higher in culture-positive vs. culture-negative samples from CF and NCF (P ϭ 0.031). A trend of an increased ratio was observed in culture-positive CF (0.590 Ϯ 0.10) compared with culture-positive NCF (0.368 Ϯ 0.085). In summary, we developed and characterized an SP-A1 gene-specific antibody and used it to identify gene-specific SP-A content in BALFs as a function of age and lung health. alveolar proteinosis; bronchoalveolar lavage fluid; cystic fibrosis; peptide antibody; surfactant protein A HUMAN SURFACTANT PROTEIN A (SP-A), a member of the C-type lectin or collectin family, is encoded by two functional genes, SP-A1 and SP-A2, with a high percentage of sequence similarity detected at the nucleotide (94%) and the amino acid (aa) (96%) levels. More than 30 alleles have been characterized for these two genes, with four SP-A1 alleles (6A, 6A 2 , 6A 3 , and 6A 4 ) and six SP-A2 alleles (1A, 1A 0 , 1A 1 , 1A 2 , 1A 3 , and 1A 5 ) most frequently observed in the general population (10,14,16,40,67). Although a high level of sequence similarity is shared among the SP-A genes and their corresponding alleles, in vitro studies have identified both qualitative (22,36,57,60,77,80,81) and quantitative (24,35,38,46,56,69,70,78,79) differences between the two genes.Qualitative differences between the SP-A1 and SP-A2 genes include functional, structural, and biochemical differences. Functionally, SP-A2 exhibits a higher level of activity than SP-A1 in its ability to enhance TNF-␣ and IL-8 production by the macrophage-like THP-1 cell line (80, 81), phagocytosis of Pseudomonas aeruginosa by rat alveolar macrophages (57), and secretion of phosphatidylcholine by type II alveolar cells (77). Structurally, circular dichroic spectroscopy stud...

show abstract

“…They showed that a pro re nata (PRN) approach to oxygen therapy at 140 days of gestation (a relatively more mature preterm infant) allowed for complete recovery from HMD and was not accompanied by clinical, radiographic, and pathological manifestations of BPD. Subsequent studies demonstrated that postnatal infection, related to endotracheal instillation of gram-negative bacteria, and/or abnormal surfactant protein A (SP-A) metabolism were important cofactors in BPD morbidity of the 140-day model (5,21).…”

Section: -Day Model ("Old Bpd")mentioning

confidence: 99%

Animal models of bronchopulmonary dysplasia. The preterm baboon models

Yoder

Coalson

2014

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Yoder BA, Coalson JJ. Animal models of bronchopulmonary dysplasia. V. The preterm baboon models. Am J Physiol Lung Cell Mol Physiol 307: L970 -L977, 2014. First published October 3, 2014 doi:10.1152/ajplung.00171.2014.-Much of the progress in improved neonatal care, particularly management of underdeveloped preterm lungs, has been aided by investigations of multiple animal models, including the neonatal baboon (Papio species). In this article we highlight how the preterm baboon model at both 140 and 125 days gestation (term equivalent 185 days) has advanced our understanding and management of the immature human infant with neonatal lung disease. Not only is the 125-day baboon model extremely relevant to the condition of bronchopulmonary dysplasia but there are also critical neurodevelopmental and other end-organ pathological features associated with this model not fully discussed in this limited forum. We also describe efforts to incorporate perinatal infection into these preterm models, both fetal and neonatal, and particularly associated with Ureaplasma/Mycoplasma organisms. Efforts to rekindle the preterm primate model for future evaluations of therapies such as stem cell replacement, early lung recruitment interventions coupled with noninvasive surfactant and high-frequency nasal ventilation, and surfactant therapy coupled with antioxidant or anti-inflammatory medications, to name a few, should be undertaken.baboon; bronchopulmonary dysplasia; lung; preterm infant; ureaplasma OF THE NEARLY 4,000,000 annual births in the United States, ϳ1% (ϳ40,000) occur at Ͻ29-wk gestation. Advances in prenatal and neonatal care have contributed to marked improvements in survival rates for these extremely immature infants, with many centers reporting survival rates Ͼ90% for infants in the 25-to 28-wk range (71). However, increasing survival of these fragile infants has been accompanied by high rates of bronchopulmonary dysplasia (BPD), the most common morbidity affecting extremely preterm infants (66,71,96). Much of the progress in improved neonatal care, particularly management of underdeveloped preterm lungs, including approaches to mechanical ventilation, surfactant therapy, and application of noninvasive respiratory support, has been derived through investigations of multiple animal models, including the neonatal baboon (Papio species). In this article we will highlight how primate models, particularly the preterm baboon model at both 140 days and 125 days gestation (term equivalent 185 days), have advanced our understanding and management of the immature human infant with neonatal lung disease; identify limitations to this and other animal models in the quest to prevent BPD; and suggest future directions to improve animal modeling and translational research to further improve outcomes. 140-Day Model ("Old BPD")The first long-term animal model for neonatal BPD in the 140-day premature baboon was developed in the early 1980s (19,26). At that time surfactant replacement therapy had not been approved for human use. Additi...

show abstract

Surfactant Proteins A and D in Premature Baboons with Chronic Lung Injury (Bronchopulmonary Dysplasia)

Cited by 67 publications

References 31 publications

Neonatal Hyperoxia Stimulates the Expansion of Alveolar Epithelial Type II Cells

Neonatal Hyperoxia Stimulates the Expansion of Alveolar Epithelial Type II Cells

Characterization of a human surfactant protein A1 (SP-A1) gene-specific antibody; SP-A1 content variation among individuals of varying age and pulmonary health

Animal models of bronchopulmonary dysplasia. The preterm baboon models

Contact Info

Product

Resources

About