Lung pathology of pale ear mouse (model of Hermansky-Pudlak syndrome 1) and beige mouse (model of Chediak-Higashi syndrome): Severity of giant lamellar body degeneration of type II pneumocytes correlates with interstitial inflammation

2005 ◽  
Vol 55 (3) ◽  
pp. 137-143 ◽  
Author(s):  
Xiaoyan Tang ◽  
Shoji Yamanaka ◽  
Yohei Miyagi ◽  
Yoji Nagashima ◽  
Yukio Nakatani
Keyword(s):  
Mouse Model ◽  
Lamellar Body ◽  
Lung Pathology ◽  
Type Ii ◽  
Beige Mouse ◽  
Interstitial Inflammation ◽  
Type Ii Pneumocytes ◽  
Hermansky Pudlak Syndrome ◽  
Chediak Higashi Syndrome

Aberrant lung structure, composition, and function in a murine model of Hermansky-Pudlak syndrome

2003 ◽  
Vol 285 (3) ◽  
pp. L643-L653 ◽  
Author(s):  
Timothy A. Lyerla ◽  
Michael E. Rusiniak ◽  
Michael Borchers ◽  
Gerald Jahreis ◽  
Jian Tan ◽  
...  
Keyword(s):  
Lamellar Body ◽  
Mutant Mice ◽  
Type Ii Cells ◽  
Lung Pathology ◽  
Type Ii ◽  
Inherited Disease ◽  
Lamellar Bodies ◽  
Age Related ◽  
Hermansky Pudlak Syndrome

Hermansky-Pudlak syndrome (HPS) is a genetically heterogeneous inherited disease causing hypopigmentation and prolonged bleeding times. An additional serious clinical problem of HPS is the development of lung pathology, which may lead to severe lung disease and premature death. No cure for the disease exists, and previously, no animal model for the HPS lung abnormalities has been reported. A mouse model of HPS, which is homozygously recessive for both the Hps1 (pale ear) and Hps2 (pearl) genes, exhibits striking abnormalities of lung type II cells. Type II cells and lamellar bodies of this mutant are greatly enlarged, and the lamellar bodies are engorged with surfactant. Mutant lungs accumulate excessive autofluorescent pigment. The air spaces of mutant lungs contain age-related elevations of inflammatory cells and foamy macrophages. In vivo measurement of lung hysteresivity demonstrated aberrant lung function in mutant mice. All these features are similar to the lung pathology described in HPS patients. Morphometry of mutant lungs indicates a significant emphysema. These mutant mice provide a model to further investigate the lung pathology and therapy of HPS. We hypothesize that abnormal type II cell lamellar body structure/function may predict future lung pathology in HPS.

Cytochemistry of type II pneumocytes in Chediak-Higashi syndrome of mice

1980 ◽  
Vol 32 (3) ◽  
pp. 290-306 ◽  
Author(s):  
Mitsuoki Eguchi ◽  
Samuel S. Spicer ◽  
Ichiro Mochizuki
Keyword(s):  
Type Ii ◽  
Type Ii Pneumocytes ◽  
Chediak Higashi Syndrome

Factors regulating lamellar body volume density of type II pneumocytes in excised dog lungs

1982 ◽  
Vol 53 (3) ◽  
pp. 555-562 ◽  
Author(s):  
J. W. Shepard ◽  
G. F. Dolan ◽  
S. Y. Yu
Keyword(s):  
Lamellar Body ◽  
Arterial Occlusion ◽  
Co2 Concentration ◽  
Volume Density ◽  
Hydrogen Ion ◽  
Body Volume ◽  
Type Ii ◽  
Type Ii Pneumocytes ◽  
Autologous Whole Blood ◽  
The Impact

Pulmonary arterial occlusion (PAO) produces multiple alterations in the physiological/biochemical environment of lung cells as well as dysfunction of the lung's surfactant system, which is considered to play a significant role in mediating lung injury. The present studies were performed using 66 excised dog lungs to evaluate the impact of alterations in ventilation, substrate availability, alveolar CO2 tension, hydrogen ion and bicarbonate concentrations, and temperature and neural denervation on the lamellar body (LB) volume density of type II pneumocytes. Ventilating excised nonperfused dog lungs with room air (0% CO2) for 4 h at 38 degrees C resulted in severe reductions (6813;77%) in LB volume density. Supplementing inspired gas with 5% CO2 prevented LB depletion, while ventilation with 2.5% CO2 moderated the severity of depletion to 17–27% of control. Ventilation with 10% CO2 tended to increase LB volume density by increasing the number of LBs per cell, whereas reductions in LB volume density predominantly resulted from a decrease in LB size. The level of ventilation had no significant effect on LB volume density independent of inspired CO2 concentration. Reducing temperature to 5 degrees C prevented LB depletion. Lung perfusion with autologous whole blood failed to moderate the severity of LB depletion during room air ventilation despite the increased availability of metabolic substrates for cellular metabolism. Adding hydrochloric acid to maintain physiologically normal hydrogen ion concentrations in the perfusing blood had a small effect in ameliorating the severity of LB depletion. These results indicate that alveolar CO2 tension and bicarbonate concentration are major factors regulating the LB content of type II pneumocytes and suggest an important link between the gas exchange and phospholipid metabolic functions of the lung.

Endocytosed SP-A and surfactant lipids are sorted to different organelles in rat type II pneumocytes

2001 ◽  
Vol 281 (2) ◽  
pp. L345-L360 ◽  
Author(s):  
Heide Wissel ◽  
Andrea Lehfeldt ◽  
Petra Klein ◽  
Torsten Müller ◽  
Paul A. Stevens
Keyword(s):  
Cell Surface ◽  
Intracellular Transport ◽  
Protein A ◽  
Lamellar Body ◽  
Surfactant Protein ◽  
Type Ii Cells ◽  
Type Ii ◽  
Lamellar Bodies ◽  
Type Ii Pneumocytes ◽  
Early Endosomes

Intracellular transport of endocytosed surfactant protein A (SP-A) and lipid was investigated in isolated rat type II cells. After internalization, SP-A and lipid are taken up via the coated-pit pathway and reside in a common compartment, positive for the early endosomal marker EEA1 but negative for the lamellar body marker 3C9. SP-A then recycles rapidly to the cell surface via Rab4-associated recycling vesicles. Internalized lipid is transported toward a Rab7-, CD63-, 3C9-positive compartment, i.e., lamellar bodies. Inhibition of calmodulin led to inhibition of uptake and transport out of the EEA1-positive endosome and thus of resecretion of both components. Inhibition of intravesicular acidification (bafilomycin A1) led to decreased uptake of both surfactant components. It inhibited transport out of early endosomes for lipid only, not for SP-A. We conclude that in type II cells, endocytosed SP-A and lipid are transported toward a common early endosomal compartment. Thereafter, both components dissociate. SP-A is rapidly recycled to the cell surface and does not enter classic lamellar bodies. Lipid is transported toward lamellar bodies.

Threshold calcium levels for lamellar body exocytosis in type II pneumocytes

1999 ◽  
Vol 277 (5) ◽  
pp. L893-L900 ◽  
Author(s):  
Thomas Haller ◽  
Klaus Auktor ◽  
Manfred Frick ◽  
Norbert Mair ◽  
Paul Dietl
Keyword(s):  
Flash Photolysis ◽  
Single Cells ◽  
Lamellar Body ◽  
Threshold Concentration ◽  
High Temporal Resolution ◽  
Alveolar Type ◽  
Type Ii ◽  
Type Ii Pneumocytes ◽  
Intracellular Ca ◽  
A Cell

Pulmonary surfactant is secreted via exocytosis of lamellar bodies (LBs) by alveolar type II cells. Here we analyzed the dependence of LB exocytosis on intracellular Ca2+concentration ([Ca2+]i). In fura 2-loaded cells, [Ca2+]iwas selectively elevated by flash photolysis of a cell-permeant caged Ca2+ compound ( o-nitrophenyl EGTA-AM) or by gradually enhancing cellular Ca2+influx. Simultaneously, surfactant secretion by single cells was analyzed with the fluorescent dye FM 1-43, enabling detection of exocytotic events with a high temporal resolution (T. Haller, J. Ortmayr, F. Friedrich, H. Volkl, and P. Dietl. Proc. Natl. Acad. Sci. USA 95: 1579–1584, 1998). Exocytosis was initiated at a threshold concentration near 320 nmol/l with both instantaneous or gradual [Ca2+]ielevations. The exocytotic response to flash photolysis was highest during the first minute after the rise in [Ca2+]iand thus almost identical to purinoceptor stimulation by ATP. Correspondingly, the effects of ATP on initial secretion could be sufficiently explained by its ability to mobilize Ca2+. This was further demonstrated by the fact that exocytosis is significantly blocked by suppression of the ATP-induced Ca2+ signal below ∼300 nmol/l. Our results suggest a highly Ca2+-sensitive step in LB exocytosis.

scholarly journals Fusion-Activated Ca2+ Entry: An “Active Zone” of Elevated Ca2+ during the Postfusion Stage of Lamellar Body Exocytosis in Rat Type II Pneumocytes

PLoS ONE ◽  
2010 ◽  
Vol 5 (6) ◽  
pp. e10982 ◽  
Author(s):  
Pika Miklavc ◽  
Manfred Frick ◽  
Oliver H. Wittekindt ◽  
Thomas Haller ◽  
Paul Dietl
Keyword(s):  
Active Zone ◽  
Lamellar Body ◽  
Type Ii ◽  
Type Ii Pneumocytes

Ca2+ entry is essential for cell strain-induced lamellar body fusion in isolated rat type II pneumocytes

2004 ◽  
Vol 286 (1) ◽  
pp. L210-L220 ◽  
Author(s):  
Manfred Frick ◽  
Cristina Bertocchi ◽  
Paul Jennings ◽  
Thomas Haller ◽  
Norbert Mair ◽  
...  
Keyword(s):  
Single Cells ◽  
Effective Strain ◽  
Lamellar Body ◽  
Alveolar Type ◽  
Type Ii ◽  
Cell Contacts ◽  
Type Ii Pneumocytes ◽  
Transient Rise ◽  
Intracellular Ca ◽  
Cell Cell

Using a new equibiaxial strain device, we investigated strain-induced Ca2+ signals and their relation to lamellar body (LB) exocytosis in single rat alveolar type II (AT II) cells. The strain device allows observation of single cells while inducing strain to the entire substratum. AT II cells tolerated high strain amplitudes up to 45% increase in cell surface area (ΔCSA) without release of lactate dehydrogenase or ATP. Strain exceeding a threshold of ∼8% ΔCSA resulted in a transient rise of the cytoplasmic Ca2+ concentration in some cells. Higher strain levels increased the fraction of Ca2+-responding cells. The occurrence of strain-induced Ca2+ signals depended on cell-cell contacts, because lone cells (i.e., cells without cell-cell contacts) did not exhibit Ca2+ signals. Above threshold, the amplitude of the Ca2+ signal as well as the number of stimulated LB fusions correlated well with the amplitude of strain. Furthermore, stimulated LB fusions occurred only in cells exhibiting a Ca2+ signal; 50 μM Gd3+ in the bath affected neither Ca2+ signals nor fusions. Intracellular Ca2+ release was triggered at higher strain amplitudes and inhibited by thapsigargin. Removal of bath Ca2+ completely inhibited Ca2+ signals and fusions. We conclude that strain of AT II cells stimulates a Ca2+ entry pathway that is highly sensitive to strain and a prerequisite for subsequent Ca2+ release. Both mechanisms result in a graded response of fusions to strain. Our data also allow us to introduce the term “effective strain” as the physiologically relevant portion of the strain amplitude.

scholarly journals Carbon Nanotube and Asbestos Exposures Induce Overlapping but Distinct Profiles of Lung Pathology in Non-Swiss Albino CF-1 Mice

2016 ◽  
Vol 44 (2) ◽  
pp. 211-225 ◽  
Author(s):  
Evan A. Frank ◽  
Vinicius S. Carreira ◽  
M. Eileen Birch ◽  
Jagjit S. Yadav
Keyword(s):  
Lung Diseases ◽  
Granulomatous Inflammation ◽  
Mechanisms Of Action ◽  
Airborne Particles ◽  
Lung Cells ◽  
Lung Pathology ◽  
Environmental Toxicants ◽  
Type Ii ◽  
Type Ii Pneumocytes ◽  
Fibrous Morphology

Carbon nanotubes (CNTs) are emerging as important occupational and environmental toxicants owing to their increasing prevalence and potential to be inhaled as airborne particles. CNTs are a concern because of their similarities to asbestos, which include fibrous morphology, high aspect ratio, and biopersistence. Limitations in research models have made it difficult to experimentally ascertain the risk of CNT exposures to humans and whether these may lead to lung diseases classically associated with asbestos, such as mesothelioma and fibrosis. In this study, we sought to comprehensively compare profiles of lung pathology in mice following repeated exposures to multiwall CNTs or crocidolite asbestos (CA). We show that both exposures resulted in granulomatous inflammation and increased interstitial collagen; CA exposures caused predominantly bronchoalveolar hyperplasia, whereas CNT exposures caused alveolar hyperplasia of type II pneumocytes (T2Ps). T2Ps isolated from CNT-exposed lungs were found to have upregulated proinflammatory genes, including interleukin 1ß (IL-1ß), in contrast to those from CA exposed. Immunostaining in tissue showed that while both toxicants increased IL-1ß protein expression in lung cells, T2P-specific IL-1ß increases were greater following CNT exposure. These results suggest related but distinct mechanisms of action by CNTs versus asbestos which may lead to different outcomes in the 2 exposure types.

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