The repair of injured alveolar type Ⅱ cell

长期吸入高浓度氧可致肺氧化性损伤,是引起早产儿支气管肺发育不良的主要原因之一.正常肺泡上皮的修复增生有赖于肺泡Ⅱ型上皮细胞的增殖和分化.高氧肺损伤治疗的根本难题在于内源性肺泡上皮不能恢复,肺组织修复过程中不能由正常的肺泡卜皮替代,而是由成纤维细胞替代.该文就肺表面活性物质、干细胞、细胞因子与肺泡Ⅱ型上皮细胞损伤修复的关系作一综述.     

The repair of injured alveolar type Ⅱ cell

长期吸入高浓度氧可致肺氧化性损伤,是引起早产儿支气管肺发育不良的主要原因之一.正常肺泡上皮的修复增生有赖于肺泡Ⅱ型上皮细胞的增殖和分化.高氧肺损伤治疗的根本难题在于内源性肺泡上皮不能恢复,肺组织修复过程中不能由正常的肺泡卜皮替代,而是由成纤维细胞替代.该文就肺表面活性物质、干细胞、细胞因子与肺泡Ⅱ型上皮细胞损伤修复的关系作一综述.     

The repair of injured alveolar type Ⅱ cell

长期吸入高浓度氧可致肺氧化性损伤,是引起早产儿支气管肺发育不良的主要原因之一.正常肺泡上皮的修复增生有赖于肺泡Ⅱ型上皮细胞的增殖和分化.高氧肺损伤治疗的根本难题在于内源性肺泡上皮不能恢复,肺组织修复过程中不能由正常的肺泡卜皮替代,而是由成纤维细胞替代.该文就肺表面活性物质、干细胞、细胞因子与肺泡Ⅱ型上皮细胞损伤修复的关系作一综述.     

肺泡Ⅱ型上皮细胞损伤修复

长期吸入高浓度氧可致肺氧化性损伤,是引起早产儿支气管肺发育不良的主要原因之一.正常肺泡上皮的修复增生有赖于肺泡Ⅱ型上皮细胞的增殖和分化.高氧肺损伤治疗的根本难题在于内源性肺泡上皮不能恢复,肺组织修复过程中不能由正常的肺泡卜皮替代,而是由成纤维细胞替代.该文就肺表面活性物质、干细胞、细胞因子与肺泡Ⅱ型上皮细胞损伤修复的关系作一综述.     

The repair of injured alveolar type Ⅱ cell

长期吸入高浓度氧可致肺氧化性损伤,是引起早产儿支气管肺发育不良的主要原因之一.正常肺泡上皮的修复增生有赖于肺泡Ⅱ型上皮细胞的增殖和分化.高氧肺损伤治疗的根本难题在于内源性肺泡上皮不能恢复,肺组织修复过程中不能由正常的肺泡卜皮替代,而是由成纤维细胞替代.该文就肺表面活性物质、干细胞、细胞因子与肺泡Ⅱ型上皮细胞损伤修复的关系作一综述.     

The repair of injured alveolar type Ⅱ cell

长期吸入高浓度氧可致肺氧化性损伤,是引起早产儿支气管肺发育不良的主要原因之一.正常肺泡上皮的修复增生有赖于肺泡Ⅱ型上皮细胞的增殖和分化.高氧肺损伤治疗的根本难题在于内源性肺泡上皮不能恢复,肺组织修复过程中不能由正常的肺泡卜皮替代,而是由成纤维细胞替代.该文就肺表面活性物质、干细胞、细胞因子与肺泡Ⅱ型上皮细胞损伤修复的关系作一综述.     

The repair of injured alveolar type Ⅱ cell

长期吸入高浓度氧可致肺氧化性损伤,是引起早产儿支气管肺发育不良的主要原因之一.正常肺泡上皮的修复增生有赖于肺泡Ⅱ型上皮细胞的增殖和分化.高氧肺损伤治疗的根本难题在于内源性肺泡上皮不能恢复,肺组织修复过程中不能由正常的肺泡卜皮替代,而是由成纤维细胞替代.该文就肺表面活性物质、干细胞、细胞因子与肺泡Ⅱ型上皮细胞损伤修复的关系作一综述.     

The repair of injured alveolar type Ⅱ cell

长期吸入高浓度氧可致肺氧化性损伤,是引起早产儿支气管肺发育不良的主要原因之一.正常肺泡上皮的修复增生有赖于肺泡Ⅱ型上皮细胞的增殖和分化.高氧肺损伤治疗的根本难题在于内源性肺泡上皮不能恢复,肺组织修复过程中不能由正常的肺泡卜皮替代,而是由成纤维细胞替代.该文就肺表面活性物质、干细胞、细胞因子与肺泡Ⅱ型上皮细胞损伤修复的关系作一综述.     

The repair of injured alveolar type Ⅱ cell

长期吸入高浓度氧可致肺氧化性损伤,是引起早产儿支气管肺发育不良的主要原因之一.正常肺泡上皮的修复增生有赖于肺泡Ⅱ型上皮细胞的增殖和分化.高氧肺损伤治疗的根本难题在于内源性肺泡上皮不能恢复,肺组织修复过程中不能由正常的肺泡卜皮替代,而是由成纤维细胞替代.该文就肺表面活性物质、干细胞、细胞因子与肺泡Ⅱ型上皮细胞损伤修复的关系作一综述.     

The repair of injured alveolar type Ⅱ cell

长期吸入高浓度氧可致肺氧化性损伤,是引起早产儿支气管肺发育不良的主要原因之一.正常肺泡上皮的修复增生有赖于肺泡Ⅱ型上皮细胞的增殖和分化.高氧肺损伤治疗的根本难题在于内源性肺泡上皮不能恢复,肺组织修复过程中不能由正常的肺泡卜皮替代,而是由成纤维细胞替代.该文就肺表面活性物质、干细胞、细胞因子与肺泡Ⅱ型上皮细胞损伤修复的关系作一综述.     

An immunohistochemical study of bronchial cells producing surfactant protein A in the developing human fetal lung

A study on immunohistochemical localization of pulmonary surfactant protein A (SP-A) in the developing human fetal lung was performed using a monoclonal antibody, PE10, against human SP-A. At 21 weeks of gestation, a few bronchial cells positive to PE10 were observed to be scattered in the main and segmental bronchi. The number of these cells appears to increase until the 32nd week of gestation, and then decrease thereafter, almost disappearing by 39 weeks. On the other hand, alveolar type II cells and Clara cells positive to PE10 began to appear at 29 weeks, increase in number until around 39 weeks, and remain constant throughout adulthood. A few bronchial glandular cells positive to PE10 were still noticed in the fetal lung. This is the first report of the presence of SP-A-containing cells in the fetal lung. This is the first report of the presence of SP-A-containing cells in the human fetal bronchial epithelium (not Clara cells in the terminal bronchiolus), proving the regularity of the sequential distribution of SP-A-containing cells in the bronchoalveolar system during pulmonary development.     

Cyclooxygenase-2 in human perinatal lung

Cyclooxygenases-1 and -2 are the key enzymes in the conversion of arachidonic acid to prostanoids. Cyclooxygenase-2 (COX-2) takes part both in inflammation and in control of cell growth. COX-2 immunohistochemistry was performed on lung tissues from autopsies, with four groups included: fetuses (n = 4, GA = 16.0 to 32.0 wk), preterm infants (n = 10, GA = 23.0 to 29.9 wk), term infants (n = 6, GA = 38.7 to 42.0 wk), and infants with bronchopulmonary dysplasia (BPD) (n = 4, GA = 28.9 to 30.7 wk). COX-2 staining occurred exclusively in the epithelial cells resembling type II pneumocytes in the alveolae, and in ciliated epithelial cells in the bronchi. In fetuses, moderate intensity alveolar staining was seen in 90-100% cells lining the alveolar epithelium. In preterm infants, high intensity alveolar staining was seen in a scattered pattern. In term infants, the alveolar staining was also scattered, but with a lower proportion of positive cells. In BPD no staining appeared in alveolar epithelial cells. The most intense bronchial staining was found in fetuses and the least intense in term infants; staining was also seen in BPD. COX-2 is present in human perinatal lung from the gestational age of 16 wk, in a changing pattern. We suggest that COX-2 may, in addition to participating in inflammation, also play a developmental role in the perinatal lung.     

Ontogeny of atrial natriuretic peptide and its receptor in the lung: effects on perinatal surfactant release

During the transition at birth to air breathing, regulation of surfactant release from alveolar type II (ATII) cells is critical. Atrial natriuretic peptide (ANP) stimulates natriuretic peptide receptor-A (NPR-A) and increases intracellular cGMP. We examined the changes in ANP and NPR-A in respiratory epithelium during the perinatal period using immunohistochemistry and studied the effect of ANP on surfactant release from ATII cells isolated from fetal and newborn lambs. NPR-A mRNA was detected in the fetal lung by Northern Blot and RT-PCR. At 100 d gestation (term 145 d), ANP staining was absent and NPR-A staining was weak in cuboidal epithelial cells. ANP and NPR-A staining was prominent in ATII cells at 136 d gestation and was undetectable postnatally. ANP stimulated (maximal effect at 10(-10)M) surfactant release from both late gestation fetal and neonatal ATII cells. Protein kinase G inhibition significantly blocked this release. We conclude that ANP stimulates surfactant release in isolated perinatal ATII cells by a cGMP-dependent mechanism. ANP and NPR-A expression in ATII cells is greatest in late gestation and declines sharply postnatally. We speculate that increased activity of the ANP/NPR-A pathway in late gestation may prime the surfactant system, preparing the lung for air breathing.     

Influence of gestational age on potential difference across fetal type II alveolar epithelium in alveolar-like structures

The active transport of ions across fetal pulmonary epithelium results in lung fluid secretion. This study investigated the potential difference (PD) across fetal type II alveolar epithelium, one of the several epithelial cell types in the fetal lung. Aggregates of these cells in alveolar-like structures (ALS) underwent microelectrode impalement to determine the effect of gestational age, and drugs on transcellular PD. In 6 ALS, the intraluminal position of the electrode was confirmed by fluorescent imaging after iontophoretic injection of Lucifer Yellow VS dye. The average PD recorded from the lumens of ALS harvested from 20-day fetal rats was 11.8 +/- (SE) 0.48 mV (lumen-negative; n = 164). Exposure to ouabain 10(-3) M significantly reduced PD from control values of 12.3 +/- (SE) 0.87 to 8.1 +/- (SE) 0.95 mV (p less than 0.01, n = 107) in ALS obtained from 20-day fetal rats. Terbutaline 10(-3) M and furosemide 10(-3) M did not influence PD. Cells obtained from fetuses near term showed a significant reduction in PD. ALS from 18-day (n = 53), 20-day (n = 164) and 22-day (n = 56) fetuses measured 13.5 +/- 0.62, 11.8 +/- 0.48 and 9.3 +/- 0.49 mV, respectively (p less than 0.05 day 18 vs. day 22). These results demonstrate that fetal type II cells grown in organotypic culture maintain a larger transcellular electrical gradient than previously reported. PD decreases with increasing gestational age and can be reduced by the Na-K ATPase inhibitor ouabain.     

In vitro transdifferentiation of human fetal type II cells toward a type I-like cell

For alveolar type I cells, phenotype plasticity and physiology other than gas exchange await further clarification due to in vitro study difficulties in isolating and maintaining type I cells in primary culture. Using an established in vitro model of human fetal type II cells, in which the type II phenotype is induced and maintained by adding hormones, we assessed for transdifferentiation in culture toward a type I-like cell with hormone removal for up to 144 h, followed by electron microscopy, permeability studies, and RNA and protein analysis. Hormone withdrawal resulted in diminished type II cell characteristics, including decreased microvilli, lamellar bodies, and type II cell marker RNA and protein. There was a simultaneous increase in type I characteristics, including increased epithelial cell barrier function indicative of a tight monolayer and increased type I cell marker RNA and protein. Our results indicate that hormone removal from cultured human fetal type II cells results in transdifferentiation toward a type I-like cell. This model will be useful for continued in vitro studies of human fetal alveolar epithelial cell differentiation and phenotype plasticity.     

Meconium increases type 1 angiotensin II receptor expression and alveolar cell death

The pulmonary renin-angiotensin system (RAS) contributes to inflammation and epithelial apoptosis in meconium aspiration. It is unclear if both angiotensin II receptors (ATR) contribute, where they are expressed and if meconium modifies subtype expression. We examined ATR subtypes in 2 wk rabbit pup lungs before and after meconium exposure and with and without captopril pretreatment or type 1 receptor (AT1R) inhibition with losartan, determining expression and cellular localization with immunoblots, RT-PCR and immunohistochemistry, respectively. Responses of cultured rat alveolar type II pneumocytes were also examined. Type 2 ATR were undetected in newborn lung before and after meconium instillation. AT1R were expressed in pulmonary vascular and bronchial smooth muscle and alveolar and bronchial epithelium. Meconium increased total lung AT1R protein approximately 3-fold (p = 0.006), mRNA 29% (p = 0.006) and immunostaining in bronchial and alveolar epithelium and smooth muscle, which were unaffected by captopril and losartan. Meconium also increased AT1R expression >3-fold in cultured type II pneumocytes and caused concentration-dependent cell death inhibited by losartan. Meconium increases AT1R expression in newborn rabbit lung and cultured type II pneumocytes and induces AT1R-mediated cell death. The pulmonary RAS contributes to the pathogenesis of meconium aspiration through increased receptor expression.