Metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in lung tissue slices from rodents and man

1998 ◽  
Vol 95 ◽  
pp. 103
Author(s):  
E. Richter ◽  
J. Engl ◽  
A.R. Tricker
Keyword(s):  
1997 ◽  
Vol 272 (3) ◽  
pp. L479-L485 ◽  
Author(s):  
M. Ikegami ◽  
T. R. Korfhagen ◽  
M. D. Bruno ◽  
J. A. Whitsett ◽  
A. H. Jobe

In the present study we asked if surfactant metabolism was altered in surfactant protein (SP) A-deficient mice in vivo. Although previous studies in vitro demonstrated that SP-A modulates surfactant secretion and reuptake by type II cells, mice made SP-A deficient by homologous recombination grow and reproduce normally and have normal lung function. Alveolar and lung tissue saturated phophatidylcholine (Sat PC) pools were 50 and 26% larger, respectively, in SP-A(-/-) mice than in SP-A(+/+) mice. Radiolabeled choline and palmitate incorporation into lung Sat PC was similar both in vivo and for lung tissue slices in vitro from SP-A(+/+) and SP-A(-/-) mice. Percent secretion of radiolabeled Sat PC was unchanged from 3 to 15 h, although SP-A(-/-) mice retained more labeled Sat PC in the alveolar lavages at 48 h (consistent with the increased surfactant pool sizes). Clearance of radiolabeled dipalmitoylphosphatidylcholine and SP-B from the air spaces after intratracheal injection was similar in SP-A(-/-) and SP-A(+/+) mice. Lack of SP-A had minimal effects on the overall metabolism of Sat PC or SP-B in mice.


2005 ◽  
Vol 98 (5) ◽  
pp. 1949-1954 ◽  
Author(s):  
R. S. Tepper ◽  
R. Ramchandani ◽  
E. Argay ◽  
L. Zhang ◽  
Z. Xue ◽  
...  

Pathophysiological conditions of the lung may shift the balance of forces so as to chronically alter the amount of strain imposed on the airways. This chronic strain could result in changes in the structure and/or function of the airways that affect its physiological properties. We evaluated the effects of imposing physiological levels of chronic mechanical strain on the passive and active physiological properties of intraparenchymal rabbit airways. Isolated bronchial segments were cultured for 48 h at transmural pressures of 0 cmH2O (No Strain) or 7 cmH2O (Strain). Effects of strain on small parenchymal airways were evaluated in lung tissue slices cultured under conditions of No Strain or ∼50% increased in diameter (Strain). Chronic strain resulted in a higher passive compliance of the bronchial segments and larger airway lumen size. In addition, bronchi not subjected to chronic Strain were more responsive to ACh than bronchi subjected to chronic Strain, and airways in lung slices subjected to No Strain narrowed more in response to ACh than airways in lung slices subjected to Strain. The greatest effects of chronic strain occurred in the smallest sized airways. Our results suggest that chronic distension of the airways has physiologically important effects on their passive and active properties, which are most prominent in the smaller, more peripheral airways.


Author(s):  
Christina Hesse ◽  
Samuel Mang ◽  
Heinz-Gerd Hoymann ◽  
Monika Niehof ◽  
Peter Braubach ◽  
...  

1978 ◽  
Vol 56 (4) ◽  
pp. 946-952 ◽  
Author(s):  
C. F. Phleger ◽  
B. S. Saunders

Minimum surface tension and phospholipid composition of fish lung and swim-bladder wash and tissue extract were determined on an obligate water breather, Hoplias malabaricus, two species of facultative air breathers, Hoplerythrinus unitaeniatus and Erythrinus erythrinus, and two species of obligate air breathers, Arapaima gigas and Lepidosiren paradoxa. In addition, lung tissue slices were incubated with [1-14C]acetale and [1-14C]palmitate.All lung and swim-bladder wash lipid extracts showed a minimum surface tension of 20–25 dyn/cm (1 dyn = 10 μN). The principle phospholipid of all species is phosphatidylcholine; no phosphatidylglycerol was detected in any sample.The two obligate air breathers had higher rates of incorporation of isotope in tissue slices than facultative air breathers and nonair breathers. This observation correlates well with the greater vascular supply to their lungs.The phospholipid patterns of these fishes are significantly different from those of mammals. We speculate that these lipids recovered from saline wash may not be important in the maintenance of lung stability. Perhaps their function is keeping water from leaking into the lung and swim bladder.


1987 ◽  
Vol 135 (6) ◽  
pp. 1334-1339 ◽  
Author(s):  
Janet S. Kerr ◽  
Claudia U. Chae ◽  
Hideaki Nagase ◽  
Richard A. Berg ◽  
David J. Riley
Keyword(s):  

Author(s):  
Carmen Amelia Molina-Torres ◽  
Oscar Noé Flores-Castillo ◽  
Irma Edith Carranza-Torres ◽  
Nancy Elena Guzmán-Delgado ◽  
Ezequiel Viveros-Valdez ◽  
...  

Abstract Background Multidrug-resistant infections due to Mycobacterium abscessus often require complex and prolonged regimens for treatment. Here, we report the evaluation of a new ex vivo antimicrobial susceptibility testing model using organotypic cultures of murine precision-cut lung slices, an experimental model in which metabolic activity, and all the usual cell types of the organ are found while the tissue architecture and the interactions between the different cells are maintained. Methods Precision cut lung slices (PCLS) were prepared from the lungs of wild type BALB/c mice using the Krumdieck® tissue slicer. Lung tissue slices were ex vivo infected with the virulent M. abscessus strain L948. Then, we tested the antimicrobial activity of two drugs: imipenem (4, 16 and 64 μg/mL) and tigecycline (0.25, 1 and 4 μg/mL), at 12, 24 and 48 h. Afterwards, CFUs were determined plating on blood agar to measure the surviving intracellular bacteria. The viability of PCLS was assessed by Alamar Blue assay and corroborated using histopathological analysis. Results PCLS were successfully infected with a virulent strain of M. abscessus as demonstrated by CFUs and detailed histopathological analysis. The time-course infection, including tissue damage, parallels in vivo findings reported in genetically modified murine models for M. abscessus infection. Tigecycline showed a bactericidal effect at 48 h that achieved a reduction of > 4log10 CFU/mL against the intracellular mycobacteria, while imipenem showed a bacteriostatic effect. Conclusions The use of this new organotypic ex vivo model provides the opportunity to test new drugs against M. abscessus, decreasing the use of costly and tedious animal models.


1973 ◽  
Vol 51 (12) ◽  
pp. 1581-1587 ◽  
Author(s):  
K. Kyei-Aboagye ◽  
D. Rubinstein ◽  
J. C. Beck

The esterification of palmitate by lung homogenates is increased by palmitoyllysolecithin in the presence of CoA and ATP. [32P]lysolecithin can also be converted to [32P]lecithin in the absence of other substrates, suggesting transacylation between two molecules of palmitoyllysolecithin. Some palmitate is esterified in the absence of added lysolecithin, ATP, and CoA. Free palmitate appears to exchange with other esterified fatty acids, especially oleate incorporated into the lecithin of lung tissue slices. The lung contains sufficient 1-palmitoyl-2-oleyllecithin for this exchange to be significant. In homogenates, Ca2+ is required for the exchange and the incorporation of palmitate. The in vivo turnover of the oleate in the lecithin of lung tissues and bronchiolar washings is more rapid than that of the palmitate. This is consistent with a mechanism of dipalmitoyllecithin synthesis involving exchange of esterified oleate for palmitate in lecithin. It is concluded that in addition to de novo synthesis of lecithin in the lung, incorporation of activated palmitate into lysolecithin and exchange of palmitate with oleate esterified in endogenous lecithin also occur. Phospholipase activity is probably involved in the latter two pathways.


Author(s):  
Valerie Beneke ◽  
Nora Grahl ◽  
Olga Danov ◽  
Sebastian Konzok ◽  
Peter Braubach ◽  
...  

2020 ◽  
Vol 55 (6) ◽  
pp. 1901346 ◽  
Author(s):  
Pierre-Marie Boutanquoi ◽  
Olivier Burgy ◽  
Guillaume Beltramo ◽  
Pierre-Simon Bellaye ◽  
Lucile Dondaine ◽  
...  

BackgroundIdiopathic pulmonary fibrosis (IPF) is a devastating disease characterised by myofibroblast proliferation and abnormal extracellular matrix accumulation in the lungs. Transforming growth factor (TGF)-β1 initiates key profibrotic signalling involving the SMAD pathway and the small heat shock protein B5 (HSPB5). Tripartite motif-containing 33 (TRIM33) has been reported to negatively regulate TGF-β/SMAD signalling, but its role in fibrogenesis remains unknown. The objective of this study was to elucidate the role of TRIM33 in IPF.MethodsTRIM33 expression was assessed in the lungs of IPF patients and rodent fibrosis models. Bone marrow-derived macrophages (BMDM), primary lung fibroblasts and 3D lung tissue slices were isolated from Trim33-floxed mice and cultured with TGF-β1 or bleomycin (BLM). Trim33 expression was then suppressed by adenovirus Cre recombinase (AdCre). Pulmonary fibrosis was evaluated in haematopoietic-specific Trim33 knockout mice and in Trim33-floxed mice that received AdCre and BLM intratracheally.ResultsTRIM33 was overexpressed in alveolar macrophages and fibroblasts in IPF patients and rodent fibrotic lungs. Trim33 inhibition in BMDM increased TGF-β1 secretion upon BLM treatment. Haematopoietic-specific Trim33 knockout sensitised mice to BLM-induced fibrosis. In primary lung fibroblasts and 3D lung tissue slices, Trim33 deficiency increased expression of genes downstream of TGF-β1. In mice, AdCre-Trim33 inhibition worsened BLM-induced fibrosis. In vitro, HSPB5 was able to bind directly to TRIM33, thereby diminishing its protein level and TRIM33/SMAD4 interaction.ConclusionOur results demonstrate a key role of TRIM33 as a negative regulator of lung fibrosis. Since TRIM33 directly associates with HSPB5, which impairs its activity, inhibitors of TRIM33/HSPB5 interaction may be of interest in the treatment of IPF.


1977 ◽  
Vol 232 (4) ◽  
pp. E358
Author(s):  
R M Evans ◽  
R W Scholz

Incorporation of tritiated water into fatty acids by rat adipose tissue and lung tissue slices incubated with 5 mM glucose indicated a level of fatty acid synthesis in rat lung approximately 15% that observed in adipose tissue in vitro. (-)-Hydroxycitrate, and inhibitor of ATP citrate lyase, markedly reduced tritiated water incorporation into fatty acids by lung tissue slices. The effects of (-)-hydroxycitrate and n-butymalonate on the incorporation of 14C-labeled glucose, pyruvate, acetate, and citrate suggested that citrate is a major acetyl carrier for de novo fatty acid synthesis in lung tissue. Alternative mechanisms to citrate as an acetyl carrier were also considered. Lung mitochondrial preparations formed significant levels of acetylcarnitine in the presence of pyruvate and carnitine. However, the effect of carnitine on the incorporation of 14C-labeled glucose, pyruvate, acetate, and citrate into fatty acids by lung tissue slices indicated that acetylcarnitine may not be a significant acetyl carrier for fatty acid synthesis but may serve as an acetyl "buffer" in the control of mitochondrial acetyl-CoA levels. Additionally, it appears unlikely that either acetylaspartate or acetoacetate are of major importance in acetyl transfer in lung tissue.


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