scholarly journals The Effect of Antisense Inhibition of Surfactant Protein a on Surfactant Protein B Expression during Human Lung Development In Vitro

1999 ◽  
Vol 45 (4, Part 2 of 2) ◽  
pp. 49A-49A
Author(s):  
John M Dagle ◽  
Troy A McCarthy ◽  
Jonathan M Klein
Keyword(s):  
Lung Development ◽  
Human Lung ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Antisense Inhibition ◽  
Surfactant Protein B ◽  
Development In Vitro ◽  
Protein B

scholarly journals Reversal of Surfactant Protein B Deficiency in Patient Specific Human Induced Pluripotent Stem Cell Derived Lung Organoids by Gene Therapy

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sandra Lawrynowicz Leibel ◽  
Alicia Winquist ◽  
Irene Tseu ◽  
Jinxia Wang ◽  
Daochun Luo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Human Lung ◽  
Induced Pluripotent Stem Cell ◽  
Surfactant Protein ◽  
Patient Specific ◽  
Surfactant Protein B ◽  
Induced Pluripotent ◽  
Protein B

Abstract Surfactant protein B (SFTPB) deficiency is a fatal disease affecting newborn infants. Surfactant is produced by alveolar type II cells which can be differentiated in vitro from patient specific induced pluripotent stem cell (iPSC)-derived lung organoids. Here we show the differentiation of patient specific iPSCs derived from a patient with SFTPB deficiency into lung organoids with mesenchymal and epithelial cell populations from both the proximal and distal portions of the human lung. We alter the deficiency by infecting the SFTPB deficient iPSCs with a lentivirus carrying the wild type SFTPB gene. After differentiating the mutant and corrected cells into lung organoids, we show expression of SFTPB mRNA during endodermal and organoid differentiation but the protein product only after organoid differentiation. We also show the presence of normal lamellar bodies and the secretion of surfactant into the cell culture medium in the organoids of lentiviral infected cells. These findings suggest that a lethal lung disease can be targeted and corrected in a human lung organoid model in vitro.

Transcription and mRNA stability regulate developmental and hormonal expression of rabbit surfactant protein B gene

1995 ◽  
Vol 268 (3) ◽  
pp. L481-L490 ◽  
Author(s):  
R. K. Margana ◽  
V. Boggaram
Keyword(s):  
Gene Transcription ◽  
Mrna Stability ◽  
Lung Development ◽  
Fetal Lung ◽  
Surfactant Protein ◽  
Mrna Levels ◽  
Fetal Lung Development ◽  
Surfactant Protein B ◽  
Protein B

Surfactant protein B (SP-B), a hydrophobic protein of pulmonary surfactant, is essential for the surface tension-reducing properties of surfactant. In the present study, we isolated and characterized cDNAs encoding rabbit SP-B, and used transcription run-on assays and Northern blot analysis to investigate the role of transcriptional and posttranscriptional mechanisms in the developmental and cAMP and dexamethasone induction of SP-B mRNA. We found two forms of SP-B cDNAs that differed by an insertion of 69 nucleotides in the 3' untranslated regions. We found that transcription across the SP-B gene is nonequimolar and the 3' end of the gene has high levels of antisense transcription. SP-B gene transcription and SP-B mRNA levels increased during fetal lung development. However, increased SP-B mRNA levels could not be accounted for primarily on the basis of increased transcription. These results suggested that enhanced SP-B gene transcription and enhanced SP-B mRNA stability mediate developmental induction of SP-B gene. In rabbit fetal lung in vitro, both dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP) and dexamethasone increased SP-B mRNA levels. DBcAMP-dependent increase in SP-B mRNA levels resulted from increased SP-B gene transcription, whereas dexamethasone-dependent increase resulted from combined effects on increased SP-B gene transcription and SP-B mRNA stability. In tissues treated with dexamethasone the half-life (t1/2) of SP-B mRNA increased > 2.5-fold (t1/2 control = 9 h; t1/2 dex-treated = 25 h). These data show that both transcription and mRNA stability regulate induction of SP-B gene expression during fetal lung development and by cAMP and dexamethasone in fetal lung in vitro.

Exposure of surfactant protein A to ozone in vitro and in vivo impairs its interactions with alveolar cells

1992 ◽  
Vol 262 (1) ◽  
pp. L63-L68 ◽  
Author(s):  
R. S. Oosting ◽  
J. F. Van Iwaarden ◽  
L. Van Bree ◽  
J. Verhoef ◽  
L. M. Van Golde ◽  
...  
Keyword(s):  
Superoxide Anion ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Alveolar Type ◽  
Type Ii ◽  
Superoxide Anion Production ◽  
Anion Production

This study focused on the question of whether exposure of surfactant protein A (SP-A) to ozone affected properties of this protein that may be involved in regulating alveolar type II cell and alveolar macrophage functions. In vitro exposure of human or canine SP-A to ozone reduced the ability of this protein to inhibit phorbol-ester induced secretion of [3H]phosphatidylcholine by alveolar type II cells in culture. Ozone-exposed human SP-A showed a decreased ability to enhance phagocytosis of herpes simplex virus and to stimulate superoxide anion production by alveolar macrophages. Experiments with elastase showed that ozone-exposed canine SP-A was more susceptible to proteolysis. A conformational change of the protein could underlie this phenomenon. Surfactant isolated from ozone-exposed rats (0.4 ppm ozone for 12 h) was also less able to stimulate superoxide anion production by alveolar macrophages than surfactant from control rats, which suggested that SP-A in vivo was also susceptible to ozone. The results of this study suggest that SP-A-alveolar cell interactions can be inhibited by ozone exposure, which may contribute to the toxicity of ozone in the lungs.

Effects of surfactant protein A and surfactant lipids on lymphocyte proliferation in vitro

1994 ◽  
Vol 267 (4) ◽  
pp. L357-L364 ◽  
Author(s):  
S. G. Kremlev ◽  
T. M. Umstead ◽  
D. S. Phelps
Keyword(s):  
Lymphocyte Proliferation ◽  
Cell Function ◽  
Immune Cell ◽  
Pulmonary Inflammation ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Inhibitory Influence ◽  
Surfactant Replacement Therapy

We studied the effects of dipalmitoyl L-alpha-phosphatidylcholine (DPPC), Survanta, surfactant protein A (SP-A), and mixtures of these substances on mitogen-induced lymphocyte proliferation using concanavalin A as a mitogen. A concentration-dependent suppression of proliferation was observed with 50-250 micrograms/ml of DPPC or Survanta. However, when SP-A was added to cultures, proliferation was stimulated. The inhibitory effects of DPPC and Survanta were altered in mixtures that contained SP-A. When added to 50 micrograms/ml of Survanta, SP-A reversed the inhibitory influence of Survanta and caused increased proliferation. These findings suggest that surfactant phospholipids cause a suppression of mitogen-induced lymphocyte proliferation, which is reversed somewhat by addition of SP-A. We hypothesize that immune cell function in the lung varies with changes in the relative amounts of surfactant components. Changes in surfactant composition may occur during pulmonary inflammation or infection or with surfactant replacement therapy and may influence immune and inflammatory processes in the lung.

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