Transgenic Mice with Glutathione Reductase Targeted to the Mitochondria of Type II Cells Are Not Riboflavin Deficient in Hyperoxia.

2009 ◽  
Author(s):  
KM Heyob ◽  
LK Rogers ◽  
SE Welty
Keyword(s):  
Transgenic Mice ◽  
Glutathione Reductase ◽  
Type Ii Cells ◽  
Type Ii ◽  
Riboflavin Deficient

A human SP-C promoter fragment targets α1-proteinase inhibitor gene expression to lung alveolar type II cells in transgenic mice

1996 ◽  
Vol 5 (2) ◽  
pp. 139-143 ◽  
Author(s):  
Eric Degryse ◽  
Maria M. De Santi ◽  
Mireille Dietrich ◽  
Dalila Ali Hadji ◽  
Jean François Spetz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transgenic Mice ◽  
Proteinase Inhibitor ◽  
Alveolar Type ◽  
Type Ii Cells ◽  
Type Ii ◽  
Alveolar Type Ii Cells ◽  
Promoter Fragment ◽  
Inhibitor Gene

TGF-α perturbs surfactant homeostasis in vivo

2005 ◽  
Vol 289 (1) ◽  
pp. L34-L43 ◽  
Author(s):  
Machiko Ikegami ◽  
Timothy D. Le Cras ◽  
William D. Hardie ◽  
Mildred T. Stahlman ◽  
Jeffrey A. Whitsett ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Transgenic Mice ◽  
Egf Receptor ◽  
Transforming Growth Factor ◽  
Dominant Negative Mutant ◽  
Type Ii Cells ◽  
Mrna Levels ◽  
Type Ii ◽  
Adult Lung ◽  
Surfactant Secretion

To determine potential relationships between transforming growth factor (TGF)-α and surfactant homeostasis, the metabolism, function, and composition of surfactant phospholipid and proteins were assessed in transgenic mice in which TGF-α was expressed in respiratory epithelial cells. Secretion of saturated phosphatidylcholine was decreased 40–60% by expression of TGF-α. Although SP-A, SP-B, and SP-C mRNA levels were unchanged by expression of TGF-α, SP-A and SP-B content in bronchoalveolar lavage fluid was decreased. The minimum surface tension of surfactant isolated from the transgenic mice was significantly increased. Incubation of cultured normal mice type II cells with TGF-α in vitro did not change secretion of surfactant phosphatidylcholine and SP-B, indicating that TGF-α does not directly influence surfactant secretion. Expression of a dominant negative (mutant) EGF receptor in the respiratory epithelium blocked the TGF-α-induced changes in lung morphology and surfactant secretion, indicating that EGF receptor signaling in distal epithelial cells was required for TGF-α effects on surfactant homeostasis. Because many epithelial cells were embedded in fibrotic lesions caused by TGF-α, changes in surfactant homeostasis may at least in part be influenced by tissue remodeling that results in decreased surfactant secretion. The number of nonembedded type II cells was decreased 30% when TGF-α was expressed during development and was increased threefold by TGF-α expression in adulthood, suggesting possible alteration of type II cells on surfactant metabolism in the adult lung. Abnormalities in surfactant function and decreased surfactant level in the airways may contribute to the pathophysiology induced by TGF-α in both the developing and adult lung.

Analysis of genomic regions involved in regulation of the rabbit surfactant protein A gene in transgenic mice

1999 ◽  
Vol 277 (2) ◽  
pp. L349-L361 ◽  
Author(s):  
Joseph L. Alcorn ◽  
Robert E. Hammer ◽  
Katherine R. Graves ◽  
Margaret E. Smith ◽  
Shanna D. Maika ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transgenic Mice ◽  
Transgene Expression ◽  
Fusion Gene ◽  
Surfactant Protein ◽  
Type Ii Cells ◽  
Type Ii ◽  
Regulation Of Expression ◽  
Camp Induction ◽  
Genomic Regions

The gene encoding surfactant protein (SP) A, a developmentally regulated pulmonary surfactant-associated protein, is expressed in a lung-specific manner, primarily in pulmonary type II cells. SP-A gene transcription in the rabbit fetal lung is increased by cAMP. To delineate the genomic regions involved in regulation of SP-A gene expression, lines of transgenic mice carrying fusion genes composed of various amounts of 5′-flanking DNA from the rabbit SP-A gene linked to the human growth hormone structural gene as a reporter were established. We found that as little as 378 bp of 5′-flanking DNA was sufficient to direct appropriate lung cell-selective and developmental regulation of transgene expression. The same region was also sufficient to mediate cAMP induction of transgene expression. Mutagenesis or deletion of either of two DNA elements, proximal binding element and a cAMP response element-like sequence, previously found to be crucial for cAMP induction of SP-A promoter activity in transfected type II cells, did not affect lung-selective or temporal regulation of expression of the transgene; however, overall levels of fusion gene expression were reduced compared with those of wild-type transgenes.

Oxidants and antioxidants in alveolar epithelial type II cells: in situ, freshly isolated, and cultured cells

1992 ◽  
Vol 262 (1) ◽  
pp. L69-L77 ◽  
Author(s):  
V. L. Kinnula ◽  
L. Chang ◽  
J. I. Everitt ◽  
J. D. Crapo
Keyword(s):  
Superoxide Dismutase ◽  
Glutathione Reductase ◽  
Cultured Cells ◽  
Ex Vivo ◽  
Antioxidant Enzyme Activities ◽  
Type Ii Cells ◽  
Type Ii ◽  
Isolated Cells ◽  
Alveolar Epithelial

Antioxidant enzyme activities, H2O2 clearance, and H2O2 generation by rat alveolar epithelial type II cells were compared between in situ, freshly isolated (6 h ex vivo), and cultured cells (48 h ex vivo). Immunocytochemical studies did not show changes in catalase, Mn superoxide dismutase, or CuZn superoxide dismutase labeling density in cytoplasm, peroxisomes, or mitochondria. Numbers of peroxisomes and mitochondria per cell decreased in cultured cells. Biochemical studies showed that cell culture resulted in a significant decrease in activities of catalase (49%), glutathione reductase (50%), glutathione peroxidase (74%), and in the capacity of the cells to scavenge extracellular H2O2. Addition of the specific catalase inhibitor, aminotriazole, decreased the rate of consumption of exogenously added H2O2 in freshly isolated cells but not in cultured cells. Neither aminotriazole nor 1,3-bis (2-chloroethyl)-1-nitrosourea, which inactivates glutathione reductase, altered H2O2 consumption by cultured cells. The rate of extracellular H2O2 release in both freshly isolated and cultured cells was 0.71 nmol.min-1.mg protein-1. It can be concluded that levels of some antioxidant enzymes fall in cultured alveolar epithelial type II cells, and that, although catalase likely plays a significant role in protection of freshly isolated cells against oxidant stress, this pathway may be less important after culture.

GM-CSF enhances lung growth and causes alveolar type II epithelial cell hyperplasia in transgenic mice

1997 ◽  
Vol 273 (4) ◽  
pp. L715-L725 ◽  
Author(s):  
Jacquelyn A. Huffman Reed ◽  
Ward R. Rice ◽  
Zsuzsanna K. Zsengellér ◽  
Susan E. Wert ◽  
Glenn Dranoff ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Transgenic Mice ◽  
Lung Epithelial Cells ◽  
Alveolar Type ◽  
Type Ii Cells ◽  
Type Ii ◽  
Cell Hyperplasia ◽  
Α Subunit ◽  
Gm Csf ◽  
Type Ii Cell

The human surfactant protein (SP)-C gene promoter was used to direct expression of mouse granulocyte macrophage colony-stimulating factor (GM-CSF; SP-C-GM mice) in lung epithelial cells in GM-CSF-replete (GM+/+) or GM-CSF null mutant (GM−/−) mice. Lung weight and volume were significantly increased in SP-C-GM mice compared with GM+/+ or GM−/− control mice. Immunohistochemical staining demonstrated marked type II cell hyperplasia, and immunofluorescent labeling for proliferating cell nuclear antigen was increased in type II cells of SP-C-GM mice. Abundance of type II cells per mouse lung was increased three- to fourfold in SP-C-GM mice compared with GM+/+ and GM−/− mice. GM-CSF increased bromodeoxyuridine labeling of isolated type II cells in vitro. Type II cells, alveolar macrophages, and endothelial and bronchiolar epithelial cells were stained by antibodies to the GM-CSF receptor α-subunit in both GM+/+ mice and GM-CSF gene-targeted mice that are also homozygous for the SP-C-GM transgene. High levels of GM-CSF expression in type II cells of transgenic mice increased lung size and caused type II cell hyperplasia, demonstrating an unexpected role for the molecule in the regulation of type II cell proliferation and differentiation.

Ultrastructure of pulmonary microvasculature in acute endotoxemia

1978 ◽  
Vol 36 (2) ◽  
pp. 470-471
Author(s):  
R. G. Gerrity ◽  
M. Richardson
Keyword(s):  
Polymorphonuclear Leukocytes ◽  
Alveolar Epithelium ◽  
Endothelial Damage ◽  
Capillary Endothelium ◽  
Type Ii Cells ◽  
Type Ii ◽  
Interstitial Edema ◽  
Pulmonary Capillaries ◽  
Lung Ultrastructure ◽  
Fibrin Thrombi

Dogs were injected intravenously with E_. coli endotoxin (2 mg/kg), and lung samples were taken at 15 min., 1 hr. and 24 hrs. At 15 min., occlusion of pulmonary capillaries by degranulating platelets and polymorphonuclear leukocytes (PML) was evident (Fig. 1). Capillary endothelium was intact but endothelial damage in small arteries and arterioles, accompanied by intraalveolar hemorrhage, was frequent (Fig. 2). Sloughing of the surfactant layer from alveolar epithelium was evident (Fig. 1). At 1 hr., platelet-PML plugs were no longer seen in capillaries, the endothelium of which was often vacuolated (Fig. 3). Interstitial edema and destruction of alveolar epithelium were seen, and type II cells had discharged their granules into the alveoli (Fig. 4). At 24 hr. phagocytic PML's were frequent in peripheral alveoli, while centrally, alveoli and vessels were packed with fibrin thrombi and PML's (Fig. 5). In similar dogs rendered thrombocytopenic with anti-platelet serum, lung ultrastructure was similar to that of controls, although PML's were more frequently seen in capillaries in the former (Fig. 6).

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