scholarly journals Protection against Acute and Chronic Hyperoxic Inhibition of Neonatal Rat Lung Development with the 21-Aminosteroid Drug U74389F

1993 ◽  
Vol 33 (6) ◽  
pp. 632-638 ◽  
Author(s):  
Lee Frank ◽  
Gwenn E Mclaughlin
1980 ◽  
Vol 188 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Janet T. Powell ◽  
Philip L. Whitney

The development of rat lung from a primitive gas-exchange organ to the mature respiratory organ is in large part a postnatal phenomenon that has been well characterized by morphological and morphometric methods. The alveolarization of the lung is achieved during the first 3 weeks of life. Cholinergic innervation of rat lung also appears postnatally. We have monitored the presence or activity of several proteins during postnatal rat lung development. Newborn-rat lung contains negligible amounts of acetylcholinesterase, but the specific activity of acetylcholinesterase reaches adult values by postnatal day 10–11. Neonatal-rat lung does not contain significant amounts of β-galactoside-binding protein [Powell (1980) Biochem. J.187, 123–129]. The activity of this endogenous lung lectin was apparent at about day 6, was maximal between days 10 and 13 before declining 8–10-fold to reach adult values. Elastin has been implicated from morphological evidence as critical to lung restructuring. We have quantified the amount of desmosine and isodesmosine per g wet wt. of lung. The concentration of elastin, by this criterion, was low and stationary until postnatal day 7; a dramatic increase in elastin concentration occurred between days 10 and 20, when adult values were reached. The peak of lung-lectin activity was coincident with the maturation of acetylcholinesterase and the beginning of rapid elastin cross-linking. The specific activities of angiotensin-converting enzyme, carbonic anhydrase, choline kinase and glucose 6-phosphate dehydrogenase were also monitored.


1995 ◽  
Vol 268 (4) ◽  
pp. L589-L595 ◽  
Author(s):  
N. Kawai ◽  
D. B. Bloch ◽  
G. Filippov ◽  
D. Rabkina ◽  
H. C. Suen ◽  
...  

Nitric oxide (NO), a potent vasodilator, is a free-radical gas synthesized from L-arginine by nitric oxide synthases (NOS). NO appears to have an important role in perinatal changes in pulmonary vascular resistance. We previously identified mRNA encoding the constitutive endothelial NOS (ceNOS) isoform in human pulmonary tissue. To begin investigating functions of this enzyme in perinatal pulmonary development, we measured ceNOS mRNA and immunoreactivity in the developing rat lung. With the use of RNA blot hybridization, abundant pulmonary ceNOS mRNA was detected during the late fetal and postnatal period. The highest levels were detected within 24 h after birth, and elevated mRNA levels persisted for 16 days. In contrast, much lower levels of ceNOS mRNA were found in adult rat lung. With the use of immunoblot techniques, ceNOS protein levels were found to be correlated with mRNA levels. To identify the pulmonary cell types expressing the ceNOS gene, in situ hybridization with a digoxigenin-labeled cRNA probe was performed on sections from lungs of 1-day-old and adult rats. In lungs from 1-day-old rats, ceNOS mRNA was detected in alveolar and serosal epithelial cells as well as in endothelial cells lining small and medium-sized blood vessels. In contrast, in adult lungs, ceNOS gene transcripts were detected in rare endothelial cells. These observations suggest that ceNOS gene expression is regulated during lung development and that ceNOS is available to participate in the postnatal reduction of pulmonary vascular resistance. ceNOS gene expression in nonendothelial cells in the neonatal rat lung suggests that NO may also contribute to nonvascular functions in the developing lung.


2000 ◽  
Vol 12 (2) ◽  
pp. 97 ◽  
Author(s):  
G. S. Maritz ◽  
H. L. Matthews ◽  
J. Aalbers

Maternal nicotine exposure interferes with the extracellular formation of the connective tissue frame-work of the neonatal lung, a process that is dependent on copper-dependent lysyl oxidase. It has been shown that, during the phase of lung development associated with alveolarization, maternal nicotine exposure resulted in a reduction in the copper content and thus conceivably in the activity of lysyl oxidase of the neonatal lung. Therefore the aims of this study were (a) to determine the effects of maternal nicotine exposure during gestation and lactation on neonatal lung development, and (b) to establish whether maternal copper supplementation during gestation and lactation prevented the effect of maternal nicotine exposure on neonatal lung development. Pregnant rats were randomly divided into four groups: the control group received saline; the second group received 1 mg nicotine (kg bodyweight)–1 day–1 subcutaneously; the third group received 1 mg copper (kg bodyweight)–1 day–1; and the fourth group received both nicotine and copper in the same quantities as the previous two groups. Lung tissue of 14- and 42-day-old rat pups were processed for light microscopy. Maternal nicotine exposure during gestation and lactation resulted in (a) decreased alveolar number, (b) reduced internal surface area and (c) increased alveolar volume. Copper supplementation during gestation and lactation prevented the adverse effects of maternal nicotine exposure during gestation and lactation on the development of the alveolar region of the rat lung.


1990 ◽  
Vol 259 (6) ◽  
pp. L415-L425 ◽  
Author(s):  
P. E. Roberts ◽  
D. M. Phillips ◽  
J. P. Mather

A novel epithelial cell from normal neonatal rat lung has been isolated, established, and maintained for multiple passages in the absence of serum, without undergoing crisis or senescence. By careful manipulation of the nutrition/hormonal microenvironment, we have been able to select, from a heterogeneous population, a single epithelial cell type that can maintain highly differentiated features in vitro. This cell type has characteristics of bronchiolar epithelial cells. A clonal line, RL-65, has been selected and observed for greater than 2 yr in continuous culture. It has been characterized by ultrastructural, morphological, and biochemical criteria. The basal medium for this cell line is Ham's F12/Dulbecco's modified Eagle's (DME) medium plus insulin (1 micrograms/ml), human transferrin (10 micrograms/ml), ethanolamine (10(-4) M), phosphoethanolamine (10(-4) M), selenium (2.5 x 10(-8) M), hydrocortisone (2.5 x 10(-7) M), and forskolin (5 microM). The addition of 150 micrograms/ml of bovine pituitary extract to the defined basal medium stimulates a greater than 10-fold increase in cell number and a 50- to 100-fold increase in thymidine incorporation. The addition of retinoic acid results in further enhancement of cell growth and complete inhibition of keratinization. We have demonstrated a strategy that may be applicable to isolating other cell types from the lung and maintaining their differentiated characteristics for long-term culture in vitro. Such a culture system promises to be a useful model in which to study cellular events associated with differentiation and proliferation in the lung and to better understand the molecular mechanisms involved in these events.


2002 ◽  
Vol 282 (3) ◽  
pp. L484-L490 ◽  
Author(s):  
Yiqiong Wang ◽  
Kaori Sakamoto ◽  
Jody Khosla ◽  
Philip L. Sannes

Chondroitin sulfates and their related proteoglycans are components of extracellular matrix that act as key determinants of growth and differentiation characteristics of developing lungs. Changes in their immunohistochemical distribution during progressive organ maturation were examined with monospecific antibodies to chondroitin sulfate, a nonbasement membrane chondroitin sulfate proteoglycan, and the specific chondroitin sulfate-containing proteoglycan decorin in whole fetuses and lungs from newborn and adult rats. Alveolar and airway extracellular matrix immunostained heavily in the prenatal rat for both chondroitin sulfate and chondroitin sulfate proteoglycan, whereas decorin was confined to developing airways and vessels. These sites retained their respective levels of reactivity with all antibodies through 1–10 days postnatal but thereafter became progressively more diminished and focal in alveolar regions. The heavy staining seen early in development was interpreted to reflect a significant and wide distribution of chondroitin sulfates, chondroitin sulfate proteoglycans, and decorin in rapidly growing tissues, whereas the reduced and more focal reactivity observed at later time points coincided with known focal patterns of localization of fibrillar elements of the extracellular matrix and a more differentiated state.


1995 ◽  
Vol 269 (4) ◽  
pp. L482-L491 ◽  
Author(s):  
Y. Zhao ◽  
S. L. Young

Tenascin (TN) is a hexameric extracellular matrix glycoprotein that may play an important role during lung development. TN protein is temporally and spatially restricted during lung organogenesis. The temporo-spatial and cellular expression of TN mRNA in lung remains unclear. Localization of message expression of TN in rat lung tissue was first investigated by using in situ hybridization performed with an antisense RNA probe. TN mRNA was present primarily within the mesenchyme of day 16 gestational age fetal rat lung tissue, whereas immunoreactive TN protein was found along the basement membrane. In postnatal day 3 rat lung tissue, TN mRNA was detected along alveolar septal walls and was concentrated at secondary septal tips. Expression of TN message was consistent with localization of immunoreactive TN protein. Accumulation of TN mRNA in alveolar septal tips suggests that mesenchyme may be the major source of TN mRNA. To investigate the cellular source of TN in rat lung, we studied the expression of TN in cultured rat lung fibroblasts, endothelial cells, and alveolar epithelial cells. Two TN isoforms having molecular mass of 230 and 180 kDa were in conditioned medium and in cellular extracts of lung fibroblasts and endothelial cells. TN was secreted and deposited in the extracellular matrix closely associated with the surface of lung fibroblasts and endothelial cells. Lung alveolar epithelial cells showed undetectable or barely detectable amounts of TN. These studies demonstrated that TN isoforms are expressed not only by lung fibroblasts but also by lung endothelial cells. The unique spatial localization of TN mRNA during lung development and expression of TN by different lung cell types suggested TN may be involved in matrix organization and cell-cell interactions during lung development.


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