Toxicity of metallic ions in the lung: Effects on alveolar macrophages and alveolar type II cells

The effect of phosphatidylglycerol on the uptake of surfactant-like liposomes by alveolar type II cells and alveolar macrophages as well as the effect on endogenous surfactant function was studied in vivo. Healthy ventilated rats were intratracheally instilled with fluorescent labeled liposomes with different concentrations of phosphatidylglycerol. Lung function was determined by monitoring arterial oxygenation and, at the end of the experiment, by recording static pressure-volume curves. In addition, alveolar cells were isolated, and cell-associated fluorescence was determined using flow cytometry. The results show that, in the presence of cofactors (Ca2+, Mg2+), phosphatidylglycerol stimulates the uptake by alveolar macrophages but hardly affects the uptake by alveolar type II cells. High concentrations of phosphatidylglycerol reduce the number of alveolar macrophages in the alveolar space and deteriorate lung function. On the other hand, the presence of cofactors protects the lung against the negative effects of phosphatidylglycerol on endogenous surfactant and alveolar macrophages. This study indicates that the phosphatidylglycerol concentration may play a fundamental role in the surfactant function and metabolism depending on the presence of so-called cofactors like calcium and magnesium; further study is needed to clarify the mechanisms involved.

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Distinct effects of SP-B and SP-C on the uptake of surfactant-like liposomes by alveolar cells in vivo and in vitro

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00054.2004 ◽

2004 ◽

Vol 287 (5) ◽

pp. L1056-L1065 ◽

Cited By ~ 10

Author(s):

D. L. H. Poelma ◽

L. J. Zimmermann ◽

W. A. van Cappellen ◽

J. J. Haitsma ◽

B. Lachmann ◽

...

Keyword(s):

Alveolar Macrophages ◽

Divalent Cations ◽

Alveolar Type ◽

Type Ii Cells ◽

Type Ii ◽

Alveolar Cells ◽

Alveolar Type Ii Cells ◽

Lipid Ratio

The effects of surfactant protein B (SP-B) and SP-C on the uptake of surfactant-like liposomes by alveolar type II cells and alveolar macrophages were studied both in vivo and in vitro. In vivo, mechanically ventilated rats were intratracheally instilled with fluorescently labeled liposomes that had SP-B and/or SP-C incorporated in different concentrations. Consequently, the alveolar cells were isolated, and cell-associated fluorescence was determined using flow cytometry. The results show that the incorporation of SP-B does not influence the uptake, and it also does not in the presence of essential cofactors. The inclusion of SP-C in the liposomes enhanced the alveolar type II cells at a SP-C to lipid ratio of 2:100. If divalent cations (calcium and magnesium) were present at physiological concentrations in the liposome suspension, uptake of liposomes by alveolar macrophages was also enhanced. In vitro, the incorporation of SP-B affected uptake only at a protein-to-lipid ratio of 8:100, whereas the inclusion of SP-C in the liposomes leads to an increased uptake at a protein-to-lipid ratio of 1:100. From these results, it can be concluded that SP-B is unlikely to affect uptake of surfactant, whereas SP-C in combination with divalent cations and other solutes are capable of increasing the uptake.

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Interaction between primary alveolar macrophages and primary alveolar type II cells under basal conditions and after lipopolysaccharide or quartz exposure

10.33915/etd.2079 ◽

2004 ◽

Author(s):

Rania S. Kanj

Keyword(s):

Alveolar Macrophages ◽

Alveolar Type ◽

Type Ii Cells ◽

Type Ii ◽

Alveolar Type Ii Cells

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In vivo and in vitro uptake of surfactant lipids by alveolar type II cells and macrophages

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00478.2001 ◽

2002 ◽

Vol 283 (3) ◽

pp. L648-L654 ◽

Cited By ~ 27

Author(s):

D. L. H. Poelma ◽

L. J. I. Zimmermann ◽

H. H. Scholten ◽

B. Lachmann ◽

J. F. van Iwaarden

Keyword(s):

Alveolar Macrophages ◽

Alveolar Type ◽

Type Ii Cells ◽

Type Ii ◽

Alveolar Cells ◽

Alveolar Type Ii Cells ◽

Small Subpopulation

The uptake of fluorescent-labeled liposomes (with a surfactant-like composition) by alveolar macrophages and alveolar type II cells was studied using flow cytometry, in vivo by instillation of the labeled liposomes in the trachea of ventilated rats followed by isolation of the alveolar cells and determination of the cell-associated fluorescence, and in vitro by incubation of isolated alveolar cells with the fluorescent liposomes. The results show that the uptake of liposomes by the alveolar cells is time and concentration dependent. In vivo alveolar macrophages internalize more than three times as many liposomes as alveolar type II cells, whereas in vitro, the amount of internalized liposomes by these cells is approximately the same. In vitro, practically all the cells (70–75%) internalize liposomes, whereas in vivo only 30% of the alveolar type II cells ingest liposomes vs. 70% of the alveolar macrophages. These results indicate that in vivo, only a small subpopulation of alveolar type II cells is able to internalize surfactant liposomes.

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Hydrogen peroxide production by alveolar type II cells, alveolar macrophages, and endothelial cells

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1991.261.2.l84 ◽

1991 ◽

Vol 261 (2) ◽

pp. L84-L91 ◽

Cited By ~ 5

Author(s):

V. L. Kinnula ◽

J. I. Everitt ◽

A. R. Whorton ◽

J. D. Crapo

Keyword(s):

Endothelial Cells ◽

Alveolar Macrophages ◽

Catalase Activity ◽

Ex Vivo ◽

Cell Protein ◽

H2o2 Production ◽

Alveolar Type ◽

Type Ii Cells ◽

Type Ii ◽

Alveolar Type Ii Cells

Extracellular H2O2 release and intracellular H2O2 production were determined in rat lung alveolar macrophages, rat alveolar type II cells, and cultured bovine aortic endothelial cells. Isolated macrophages (5 h ex vivo) released 3.1 +/- 0.09 nmol H2O2.min-1.mg cell protein-1, freshly isolated (5 h ex vivo) type II cells released 0.7 +/- 0.07 nmol H2O2.min-1.mg protein-1, and cultured endothelial cells released 0.06 +/- 0.005 nmol H2O2.min-1.mg protein-1. The rate of extracellular H2O2 release decreased rapidly over time in both fresh macrophages and freshly isolated type II cells. When the measurements were repeated at different times ex vivo, the decrease was greater than 20%/h, and H2O2 release was almost undetectable 12 h ex vivo. The decrease occurred while lactate dehydrogenase release, catalase activity, and intracellular H2O2 production remained unchanged. Catalase activity was 59.3 +/- 4.9 nmol O2 produced.min-1.mg protein-1 in type II cells, 13.2 +/- 1.8 in macrophages, and 11.4 +/- 2.7 in endothelial cells. Aminotriazole is a compound that inhibits catalase in the presence of H2O2 at a rate that is proportional to the rate of intracellular H2O2 production in or near peroxisomes. Incubation of the cells with aminotriazole led to a rapid inhibition of catalase. In 15 min the reduction of catalase activity was 69% in type II cells, 53% in macrophages, and 37% in endothelial cells. When freshly isolated type II cells were exposed to hyperoxia (95% O2) for 30 min, no changes in the rate of either intracellular H2O2 production or extracellular H2O2 release were seen.

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