The air-blood barrier represents the maturity of developing lung. The development of air-blood barrier in human fetal lung was studied by transmission electron microscopy. The results obtained were as follows. 1. The formation of air-blood barrier started at 16 week of postcoitum, which was the end of pseudoglandular period. The basement membranes began to be fused with each other as the capillaries penetrated between epithelial cells of primitive alveoli. 2. The flattening of the type II alveolar cells was observed only around the site of fused basement membranes, which seemed to be developed not by mechanical force but by induction of the fused basement membrane. 3. The basement membranes of capillaries and alveoli were relatively flat until the fusion occurred, but they showed severe folds with the occurrence of fusion. But with the proceeding of the terminal sac period, the folds greatly decreased. In summary, the air-blood barrier began to develop at the end of pseudoglandular period and was formed as capillaries penetrated the cytoplasms of epithelial cells devoided of the nuclei. The fused basement membranes seems to play an important role in the development of air-blood barrier.
Basement Membrane ; Blood-Air Barrier* ; Capillaries ; Cytoplasm ; Epithelial Cells ; Humans* ; Lung* ; Microscopy, Electron, Transmission ; Pulmonary Alveoli

OBJECTIVE: To comparatively study the toxicity of four metal-containing nanoparticles (MNPs) and their chemical counterparts to the air-blood barrier (ABB) permeability using an in vitro model. METHODS: ABB model, which was developed via the co-culturing of A549 and pulmonary capillary endothelium, was exposed to spherical CuO-NPs (divided into CuO-40, CuO-80, and CuO-100 based on particle size), nano-Al2O3 (sheet and short-rod-shaped), nano-ZnO, nano-PbS, CuSO4, Al2(SO4)3, Zn(CH3COO)2, and Pb(NO3)2 for 60 min. Every 10 min following exposure, the cumulative cleared volume (ΔTCL) of Lucifer yellow by the model was calculated. A clearance curve was established using linear regression analysis of ΔTCL versus time. Permeability coefficient (P) was calculated based on the slope of the curve to represent the degree of change in the ABB permeability. RESULTS: The results found the increased P values of CuO-40, CuO-80, sheet, and short-rod-shaped nano-Al2O3, Al2(SO4)3, and Pb(NO3)2. Among them, small CuO-40 and CuO-80 were stronger than CuO-100 and CuSO4; no difference was observed between Al2(SO4)3 and sheet and short-rod-shaped nano-Al2O3; and nano-PbS was slightly weaker than Pb(NO3)2. So clearly the MNPs possess diverse toxicity. CONCLUSION ABB permeability abnormality means pulmonary toxicity potential. More studies are warranted to understand MNPs toxicity and ultimately control the health hazards.
A549 Cells ; Blood-Air Barrier ; metabolism ; Epithelium ; metabolism ; Humans ; Metal Nanoparticles ; toxicity ; Particle Size ; Permeability

BACKGROUND: Lung pericytes are important constituent cells of blood-air barrier in pulmonary microvasculature. These cells take part in the control of vascular contractility and permeability. In this study, it was hypothesized that change of lung pericytes might be attributable to pathologic change in microvasculature in acute lung injury. The purpose of this study was how hypoxia change proliferation and genetic expression in lung pericytes. METHODS: From the lungs of several Sprague-Dawley rats, performed the primary culture of lung pericytes and subculture. Characteristics of lung pericytes were confirmed with stellate shape in light microscopy and immunocytochemistry. 2% concentration of oxygen and 200muM CoCl2 were treated to cells. Tryphan blue method and reverse transcription-polymerase chain reaction were done. RESULTS: 1. We established methodology for primary culture of lung pericytes. 2. Hypoxia inhibited cellular proliferation in pericytes. 3. Hypoxia could markedly induce vascular endothelial growth factor(VEGF) and smad-2. 4. Hypoxia-inducible factor-1alpha (HIF-1alpha)was also induced by 2% oxygen. CONCLUSION: Viability of lung pericytes are inhibited by hypoxia. Hypoxia can stimulate expression of hypoxia-responsive genes. Pericytic change may be contributed to dysfunction of alveolar-capillary barrier in various pulmonary disorders.
Acute Lung Injury ; Anoxia ; Blood-Air Barrier ; Cell Proliferation ; Immunohistochemistry ; Lung* ; Microscopy ; Microvessels ; Oxygen ; Pericytes* ; Permeability ; Rats, Sprague-Dawley ; Vascular Endothelial Growth Factor A

BACKGROUND: Laminin-1 is known to have regular functions in the development and course of differentiation of the lungs. The morphogenesis and distribution of laminin-1 still remains as a mystery and its distribution and changes in the molecular structure of laminin-1 in the pathogenesis of the lung still is a subject of great controversy. In this study, experiments were done to delineate the distribution and changes in the amount of laminin-1 after inducing inflammation of the lungs by exposing experimental animals to CS gas and especially, to find compositions of laminin-1 within type II pneumocytes. MATERIALS AND METHODS: The experimental subjects of study were newborn rats and the extracted tissue from the experimental rats were viewed under light microscope and electron microscope after the sections were treated with immunohistochemical methods and immunogold reaction methods using bounded gold particles. RESULTS: 1) Lymphocytes and mononuclear phagocytes invaded the alveolar septa in the 2 day group rats after CS gas exposure and intense interstitial inflammation was seen in the 3 day group. 2) Laminin immunoreactions decreased to a moderate degree in the 2 and 3 day group rats after CS gas exposure and strong laminin immunoreactions were seen again in the 5 and 7 day group rats. 3) Gold particles in basal lamina of the lung blood-air barrier decreased and in the type I pneumocytes decreased in the 2 and 3 day group rats after CS gas exposure. 4) Gold particles were seen only on the surface of the cell membranes of type II pneumocytes of the 1 and 2 day group rats after CS gas exposure. 5) Few gold particles around the lamellar bodies and cytoplasm of type II pneumocytes in the control rat group and at 12 hours after CS gas exposure. Gold particles are seen only on the surface of type II pneumocytes of the 1 and 2 day group rats after CS gas exposure and are evenly distributed in small amounts in the cells of the 3 day group after CS gas exposure. CONCLUSION: CS gas exposure in the rats caused inflammation of lung alveolar septa and also induced a decrease in laminin-1 in basal lamina and loss of laminin-1 in the cytoplasm of type II pneumonocytes. As the inflammatory cells disappeared, an increase in the distribution of laminin-1 occurred. This reflects tissue regeneration functions of laminin-1 in the pneumocytes of rats and the distribution of laminin-1 in type II pneumocytes can be seen through the electron microscope using immunogold methods.
Animals ; Basement Membrane ; Blood-Air Barrier ; Cell Membrane ; Cytoplasm ; Humans ; Infant, Newborn ; Inflammation ; Laminin ; Lung* ; Lymphocytes ; Molecular Structure ; Morphogenesis ; Phagocytes ; Pneumocytes ; Rats* ; Regeneration

OBJECTIVETo investigate the protective effects of bactericidal/permeability increasing protein simulated peptide (bactericidal neutralizing endotoxin protein, BNEP) on murine acute lung injury (ALI) induced by lipopolysaccharide (LPS).

METHODSA murine model of ALI was reproduced by lipopolysaccharide via intranasal instillation. The Balb/c mice were randomly divided into control (n = 20, with nasal instillation of isotonic saline), LPS instillation (n = 20, with nasal instillation of isotonic saline and LPS) and BNEP treatment (n = 20, with nasal instillation of isotonic saline plus LPS and BNEP) groups. The ratio of lung wet weight to dry weight, the permeability of pulmonary capillary vessels and the histopathology of pulmonary tissue were determined in all groups. The change in the expression of Toll-like receptor 2 and 4 (TLR2/4) in the pulmonary tissue was detected by immunohistochemistry.

RESULTSCompared with LPS instillation group, the ratio of lung wet weight to dry weight and the permeability of pulmonary capillary vessel was decreased significantly in the BNEP group, and the inflammatory infiltration in the pulmonary tissue induced by neutrophil influx was alleviated markedly with BNEP treatment. The expression of TLR2 and TLR4 in pulmonary vascular endothelial cells, macrophages and alveolar type II epithelial cells in BNEP group were lower than those in LPS group (TLR2: 128 +/- 10 vs 214 +/- 12, P < 0.01).

CONCLUSIONBNEP, as a simulated peptide of BPI, exerted a remarkable protective effect on ALI induced by LPS.

Acute Lung Injury ; chemically induced ; pathology ; physiopathology ; Animals ; Antimicrobial Cationic Peptides ; pharmacology ; Blood Proteins ; pharmacology ; Blood-Air Barrier ; Capillary Permeability ; Disease Models, Animal ; Lipopolysaccharides ; adverse effects ; Lung ; pathology ; Mice ; Mice, Inbred BALB C

OBJECTIVETo observe the effect of sevoflurane on membrane permeability of alveolar capillaries in rats with acute lung injury and the ratio of inflammatory cells in bronchoalveolar lavage fluid in rats with acute endotoxin lung injury.

METHODS48 Wistar rats were selected and divided into group C, L, S1L and S2L after injection evans blue 50 mg/kg in random with 12 rats in each group. Group C was taken as control group, 1.2 ml normal saline was injected into the rats via femoral vein and then the rats were mechanically ventilated for 4 hours; The rats in group L were also mechanically ventilated for 4 hours after injection of endotoxin 5 mg/kg via the same vein. For the rats in group S1L and S2L, 1.0 or 1.5 minimal alveolar concentration (MAC) sevoflurane was inhaled with mechanical ventilation after injection of endotoxin 5 mg/kg. Evans blue was not injected into 6 rats of each group in order that the 6 rats could be used for pathological examination and alveoli lavage, lung pathomorphological score of the lung, lung wet/dry weight ratio, the content of lung water, lung permeability index, content of evans blue, total amount and ratio of inflammatory cells in bronchoalveolar lavage fluid (BALF) were all determined.

RESULTSSevoflurane of 1.0 MAC and 1.5 MAC made lung wet/dry weight ratio and content of lung water change insignificantly; lung permeability index, content of evans blue and pathomorphological score in group S1L decreased from 4.86 +/- 0.82, 112.21 +/- 11.44 ng/mg, 9.17 +/- 0.90 to 3.98 +/- 0.50, 92.85 +/- 11.80 ng/mg, 7.50 +/- 0.96; group S2L decreased to 3.91 +/- 0.34, 96.33 +/- 8.79 ng/mg, 7.67 +/- 0.75. Sevoflurane of 1.0 MAC and 1.5 MAC did not have a significantly effect on total amount and ratio of inflammatory cells in BALF.

CONCLUSIONMembrane permeability of alveolar capillaries after acute endotoxin lung injury decreased by inhalation of sevoflurane of 1.0 MAC and 1.5 MAC and pathological injury of lung tissue relieved.

Animals ; Blood-Air Barrier ; drug effects ; physiology ; Bronchoalveolar Lavage Fluid ; cytology ; Capillary Permeability ; drug effects ; physiology ; Endotoxins ; toxicity ; Female ; Male ; Methyl Ethers ; pharmacology ; Rats ; Rats, Wistar ; Respiratory Distress Syndrome, Adult ; chemically induced ; pathology ; physiopathology

Industrial glues contain many kinds of organic solvents and glue sniffing by young people has become a social problem in Korea. Glue vapor may induce chronic toxicities different from those induced by exposures to the solvent of single component. We studied the effects of the inhalation of glue vapor on the primary target organ, the pulmonary epithelium of the respiratory system. Vapor samples of glue were collected for analysis; the components were acetone, n-hexane, methyl cyclopentane, c-hexane, and toluene. For the inhalation of glue vapor, experimental mice were exposed in a whole body chamber for 20 min/d for 3, 5, 7, and 14 d. Control groups were exposed to room air. Animals were euthanized and lung tissues were fixed in 10% neutral formalin for light microscopy, and in 2.5% glutaraldehyde plus 1.5% paraformaldehyde for electron microscopy. The results are as follows. 1. Alcianophilic bands were not detected in the normal alveolar epithelium, but weak alcianophilic bands were detected in bronchioles. Alcian blue-PAS and PAS positive cells were found in the mucosae of mice exposed to glue vapor for 5 and 7 d. 2. Types I and II pneumocytes and capillary endothelial cells were found in the normal alveolar epithelium. The blood-air barrier consists of Type I pneumocytes, a common basal lamina, and the capillary endothelium. 3. The alveolar epithelium of vapor-exposed mice showed more type II pneumocytes. In the longerexposed group, Type I pneumocytes and endothelial cells contained many pinocytotic vesicles. 4. The vapor-exposed lungs showed macrophages in the alveolar space, mild interstitial swelling, and increased numbers of collagenous fibers. Clearly, ultrastructural changes in pulmonary epithelia can occur following glue sniffing.
Acetone ; Adhesives ; Animals ; Basement Membrane ; Blood-Air Barrier ; Bronchioles ; Collagen ; Cyclopentanes ; Endothelial Cells ; Endothelium, Vascular ; Epithelium ; Formaldehyde ; Glutaral ; Inhalant Abuse ; Inhalation* ; Korea ; Lung* ; Macrophages ; Mice* ; Microscopy ; Microscopy, Electron ; Mucous Membrane ; Pneumocytes ; Respiratory System ; Social Problems ; Solvents ; Toluene

The term “particulate Matter (PM)” refers to the mixture of small-sized solid particles and liquid droplets floating in the air, and is referred to as PM₁₀ ( < 10 µm), PM(2.5) ( < 2.5 µm) and PM(1.0). Much PM is an anthropogenic substance generated by transportation or industrial activities, which is transformed into a second toxic substance by chemical reactions in the atmosphere. PM reaches the brain directly through olfactory transport, or through the blood-brain barrier during systemic circulation. PM that enters the local cerebral circulation causes neuroinflammation through microglial cells and endotoxins. According to previous studies, greater PM exposure results in lower brain volume, especially white matter. Among neurodevelopmental disorders, the correlation between the occurrence of autism spectrum disorder and exposure to PM is widely known. Other studies have found that exposure to PM was associated with low cognitive function and increased rate of cognitive aging. PM can also cause pathology of early Alzheimer's disease and increases the risk of Alzheimer's dementia and mild cognitive impairment.
Air Pollution ; Alzheimer Disease ; Atmosphere ; Autism Spectrum Disorder ; Blood-Brain Barrier ; Brain ; Cerebrovascular Circulation ; Cognition ; Cognitive Aging ; Dementia ; Endotoxins ; Mild Cognitive Impairment ; Neurodevelopmental Disorders ; Particulate Matter ; Pathology ; Transportation ; White Matter