Rats fed on a vitamin E-deficient diet (E-depleted group) and a vitamin E-supplemented diet (E-supplemented group) were exposed to 0.3 ppm ozone for three hours daily, five days a week for seven months. Then animals from each group were sacrificed, and electron microscopic studies on the lung and biochemical examinations on the lung and liver were performed. 1) Vitamin E concentration in serum decreased following ozone exposure in the E-supplemented group, whereas it remained unaffected in the E-depleted group. 2) Both TBA value and % release of lysosomal enzyme (acid phosphatase) of the liver were increased in vitamin E-depleted air-exposed rats, and showed even higher values following ozone exposure. Levels of both components were highest in the vitamin E-depleted ozone-exposed rats, thus demonstrating that there are a marked increase in lipid peroxide and the increased labilization of lysosomes in this instance. 3) Arachidonic acid (20:4) of total lipid, phospholipid and lecithin in the lung tissue showed a tendency to decrease in vitamin E-depleted air-exposed rats. Those in the ozone-exposed animals showed in both groups a tendency to increase in total lipid and lecithin, and to decrease in phospholipid. However, a change in the fatty acid composition following ozone exposure was generally mild. 4) The fatty acid composition of phospholipid in lung washings did not show a remarkable change following ozone exposure in either group, thus suggesting that it has the resistivity to oxidation. 5) Morphological observations on the lung with the scanning and transmission electron microscopes did not reveal any clear differences between the two groups. The defensive effect of vitamin E on ozone toxicity induced by long-term exposure to ozone was not made clear by the morphological or biochemical examination of the lung. However, biochemical findings in liver of rats exposed to ozone suggested the possibility that vitamin E deficiency permits the damaging effects of lipid peroxidation on biological membranes.
To clarify the role of bradykinin receptor subtypes, we examined the effect of bradykinin on feline tracheal and human airway submucosal gland secretion using an isolated gland preparation. Bradykinin induced a significant increase in [3H]glycoconjugate secretion in a dose-dependent manner from isolated glands, which was significantly inhibited by D-Arg-(Hyp3, Thi5,8, D-Phe7)-bradykinin (the B2-receptor antagonist), whereas Des-Arg9-(Leu8)-bradykinin (B1-receptor antagonist) or indomethacin did not significantly alter it. Nitric oxide synthase inhibitor (nitro-L-arginine methyl ester) caused a significant inhibition of bradykinin-induced glycoconjugate secretion, which was reversed by the addition of L-arginine. Bradykinin evoked bidirectional current responses, and an initial inward current (Cl- current) was followed by an outward current (K+ current) of the acinar cells in a whole cell configuration by patch-clamp technique. Bradykinin induced an immediate increase in intracellular calcium concentration ([Ca2+]i) of the acinar cells followed by a prolonged plateau, and Ca2+ removal resulted in an initial increase alone. [Ca2+]i rise was significantly inhibited by the B2-receptor antagonist, whereas the B1-receptor antagonist did not significantly alter it. These findings suggest that B2-receptor stimulation and the resultant [Ca2+]i rise induced both mucus glycoprotein and electrolyte secretions, involving NO formation in airway submucosal gland cells.
To determine what muscarinic receptor subtype regulates [Ca2+]i mediating airway submucosal gland secretion, we examined the effects of atropine (Atr), pirenzepine (PZ), 11([2-(diethylamino)methyl-1-piperidinyl] acetyl)-5,11-dihydro-6H-pyrido (2,3-b)(1,4)-benzo-diazepin-6-one (AF-DX116) and 4-diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP) on methacholine (MCh)-evoked [Ca2+]i rise in acinar cells, and compared this with mucus glycoprotein (MGP) and electrolyte secretion evoked by MCh from submucosal glands isolated from feline trachea. [Ca2+]i was measured with the Ca(2+)-sensitive fluorescent dye, fura 2. We determined MGP secretion by measuring TCA-precipitable 3H-labeled glycoconjugates and electrolyte secretion by the change in the rate constant of 22Na-efflux from isolated glands. Half-maximal inhibitory concentrations (IC50) of PZ, AF-DX116, 4-DAMP, and Atr against MCh-evoked [Ca2+]i rise were 10(-7) M, 6 x 10(-6) M, 8 x 10(-9) M, and 6 x 10(-9) M, respectively. IC50 of PZ, AF-DX116, 4-DAMP, and Atr against MCh-evoked MGP secretion were 10(-6) M, 2 x 10(-5) M, 8 x 10(-9) M, and 6 x 10(-9) M, respectively. MCh (10(-5) M)-evoked 22Na efflux was significantly inhibited by 10(-7) M 4-DAMP and 10(-7) M Atr (P less than 0.01, each) but not by 10(-7) M PZ. Receptor binding assays with [3H]quinuclidinyl benzilate showed that the Ki values for PZ, AF-D x 116, 4-DAMP and Atr were 2.2 x 10(-8) M, 6.6 x 10(-7) M, 6.2 x 10(-10) M, and 2.9 x 10(-10) M, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Five idiopathic pulmonary fibrosis (IPF) patients with sputum since the initial period of the disease (IPF SP+, more than 15 ml/day) were compared with five IPF patients without sputum throughout the course of the disease (IPF SP-) and four control subjects without pulmonary disease matched for age and sex. No significant differences in the duration of symptoms, pulmonary functions, or glucocorticoid therapy were observed between the two IPF groups. Autopsied lungs fixed by immersion into formaldehyde were used for morphometry by digitizing computer. The volume proportion of glands to bronchial wall thickness (gland%), volume proportion of goblet cells to total epithelial layer (goblet%), and luminal mucous volume were measured in central and peripheral airways. The gland percentage in the central airways of the IPF SP+ group was 18 +/- 1% (mean +/- SE), which was significantly greater than 7 +/- 0.6% of the IPF SP- group (p less than 0.001), similar to the 6 +/- 1% of control subjects. Luminal mucous volume in the peripheral airways of the IPF SP+ group was 11 +/- 2%, which was significantly greater than 3 +/- 1% of the IPF SP- group (p less than 0.05) or 0.6 +/- 0.3% of the control subjects (p less than 0.01). Furthermore, luminal mucous volume in both the central and peripheral airways significantly correlated with gland% (p less than 0.01, each). No significant difference in other parameters such as goblet% and cell infiltration between the IPF SP+ group and IPF SP- group was observed. These findings suggest that IPF with hypersecretion is associated with mucous glandular hypertrophy and the accumulation of mucus in the airways.
Abstract The effects of ageing on the numbers of alveolar pores of Kohn and on the cytoplasmic components of alveolar type II cells were studied in monkey lungs by scanning and transmission electron microscopy. Lung tissue from 26 female and three male pigtail macaques whose ages ranged from 1 month to 31 years (life span is 35 years) was analysed. From the age of 1 month to 10 years there was a significant increase in the number of alveolar pores ( r = 0·85, p < 0·001); however, between the ages of 14 years to 31 years there was no significant change. In seven animals ranging in age from 1 month to 4 years (mean 2·4 years) the number of pores was 5·8 ± 3·9 (mean · S.D.), whereas in 10 animals aged 16 to 31 years (mean 20·3 years) the number of pores was 32·7 ± 17·5 (mean ± S.D.) per alveolar profile, a significant difference ( p < 0·002). In older animals (15–20 years) there was a significant decrease, both in the number of lamellar bodies per alveolar type II cell ( p < 0·01) and in the volume density of lamellar bodies to cytoplasmic volume ( p < 0·05) compared with young animals (1 month to 4·8 years). In older animals, there was also a significant increase in the volume density of a vacuole‐like dilatation of the endoplasmic reticulum in alveolar type II cells ( p < 0·05) compared with young animals. These findings suggest impaired pulmonary surfactant production with aging. Both the increased number of alveolar pores and the postulated decrease of surfactant production could play a role in the pathogenesis of pulmonary emphysema.
Normal Chest Radiograph and Lung Function do not Necessarily MeanNormal LungsVarious systemic diseases or disorders involve the lungs but the initial involvement does not always reveal abnormal findings of chest radiograph or pulmonary function.The early stage
