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

Poelma, D. L. H.; Zimmermann, Luc J. I.; Scholten, H. H.; Lachmann, Burkhard; Iwaarden, J. Freek van

doi:10.1152/ajplung.00478.2001

Cited by 31 publications

(38 citation statements)

References 19 publications

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“…Using a nondegradable analog of dipalmitoylphosphatidylcholine or flow cytometry, others found that although macrophages take up liposomes in vivo, type II cells make a greater contribution to the uptake and metabolism of lipids (35,37). In this study, we found radioactivity associated with macrophages and type II cells after instillation of 125 I-SP-A and perfusion of the lung for 1 h followed by isolation of the cells.…”

Section: )supporting

confidence: 52%

Pathways for clearance of surfactant protein A from the lung

Jain¹,

Dodia²,

Fisher³

et al. 2005

American Journal of Physiology-Lung Cellular and Molecular Phys

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Uptake and degradation of 125 I-surfactant protein A (SP-A) over a 1-h period was studied in alveolar cells in culture and in isolated perfused lungs to elucidate the mechanism for clearance of the protein from the alveolar space. Specific inhibitors of clathrin-and actin-dependent endocytosis were utilized. In type II cells, uptake of SP-A, compared with controls, was decreased by 60% on incubation with clathrin inhibitors (amantadine and phenylarsine oxide) or with the actin inhibitor cytochalasin D. All agents reduced SP-A metabolism by alveolar macrophages. Untreated rat isolated perfused lungs internalized 36% of instilled SP-A, and 56% of the incorporated SP-A was degraded. Inhibitors of clathrin and actin significantly reduced SP-A uptake by ϳ54%, whereas cytochalasin D inhibited SP-A degradation. Coincubation of agents did not produce an additive effect on uptake of SP-A by cultured pneumocytes or isolated perfused lungs, indicating that all agents affected the same pathway. Thus SP-A clears the lung via a clathrin-mediated pathway that requires the polymerization of actin.

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Section: )supporting

confidence: 52%

Pathways for clearance of surfactant protein A from the lung

Jain¹,

Dodia²,

Fisher³

et al. 2005

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…However, although the effects of PC16:0/14:0 were concentration dependent and mostly required an uptake during 48 h preincubation, the amount of PC16:0/14:0 taken up into macrophages from Curosurf approximated that of the isolated compound given as liposomes. The principle difference in uptake between Curosurf and PC species might be due to lipophilic SP-B and SP-C, anionic PGs, and neutral lipids being present in animalderived surfactants (17). However, our data demonstrate that internalization of either compound is an active process, because it was blunted at 4jC (Fig.…”

Section: Discussionmentioning

confidence: 59%

“…The organic phase was mixed with Curosurf or PC species in a molar ratio of 5:95 (17) and dried under a stream of nitrogen. Lissamine-DHPE-labeled liposomes were analyzed by FACS.…”

Section: Preparation Of Lissamine-dhpe-labeled Liposomes and Assessmementioning

confidence: 99%

Differential effect of surfactant and its saturated phosphatidylcholines on human blood macrophages

Gille

Spring

Bernhard

et al. 2007

Journal of Lipid Research

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Blood monocyte-derived macrophages invading the alveolus encounter pulmonary surfactant, a phospholipoprotein complex that changes composition during lung development. We tested the hypothesis that characteristic phosphatidylcholine (PC) components differentially influence macrophage phenotype and function, as determined by phagocytosis of green fluorescent protein-labeled Escherichia coli and aCD3-induced T cell proliferation. Human macrophages were exposed to surfactant (Curosurf:), to two of its characteristic phosphadidylcholine (PC) components (dipalmitoyl-PC and palmitoylmyristoyl-PC), and to a ubiquituous PC (palmitoyloleoyl-PC) as control. Interaction of Curosurf and PC species with macrophages was assessed using Lissaminei-dihexadecanoyl-phosphoethanolaminelabeled liposomes. Curosurf and both saturated surfactant PC species downregulated CD14 expression and upregulated CD206. HLA-DR and CD80 were upregulated by Curosurf and palmitoylmyristoyl-PC, whereas dipalmitoyl-PC showed no effect. The latter upregulated TLR2 and TLR4 expression, whereas Curosurf and palmitoylmyristoyl-PC had no effect. PC species tested were incorporated in comparable amounts by macrophages. Curosurf and PC species inhibited phagocytosis of E. coli. Scavenger receptor CD36, CD68, SR-A, and LOX-1 mRNA expression was upregulated by Curosurf, whereas PC species only upregulated SR-A. Curosurf and palmitoylmyristoyl-PC inhibited aCD3-induced T cell proliferation by 50%, whereas dipalmitoyl-PC and palmitoyloleoyl-PC showed no effect. These data identify individual surfactant PC species as modifiers of macrophage differentiation and suggest differential effects on innate and adaptive immune

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“…Liposomes were prepared as described previously (24). Details are provided in the online supplement.…”

Section: Liposome Preparationmentioning

confidence: 99%

A Pneumocyte–Macrophage Paracrine Lipid Axis Drives the Lung toward Fibrosis

Romero¹,

Shah²,

Duong³

et al. 2015

Am J Respir Cell Mol Biol

125

107

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Lipid-laden macrophages, or "foam cells," are observed in the lungs of patients with fibrotic lung disease, but their contribution to disease pathogenesis remains unexplored. Here, we demonstrate that fibrosis induced by bleomycin, silica dust, or thoracic radiation promotes early and sustained accumulation of foam cells in the lung. In the bleomycin model, we show that foam cells arise from neighboring alveolar epithelial type II cells, which respond to injury by dumping lipids into the distal airspaces of the lungs. We demonstrate that oxidized phospholipids accumulate within alveolar macrophages (AMs) after bleomycin injury and that murine and human AMs treated with oxidized phosphatidylcholine (oxPc) become polarized along an M2 phenotype and display enhanced production of transforming growth factor-b1. The direct instillation of oxPc into the mouse lung induces foam cell formation and triggers a severe fibrotic reaction. Further, we show that reducing pulmonary lipid clearance by targeted deletion of the lipid efflux transporter ATPbinding cassette subfamily G member 1 increases foam cell formation and worsens lung fibrosis after bleomycin. Conversely, we found that treatment with granulocyte-macrophage colony-stimulating factor attenuates fibrotic responses, at least in part through its ability to decrease AM lipid accumulation. In summary, this work describes a novel mechanism leading to foam cell formation in the mouse lung and suggests that strategies aimed at blocking foam cell formation might be effective for treating fibrotic lung disorders.

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

Cited by 31 publications

References 19 publications

Pathways for clearance of surfactant protein A from the lung

Pathways for clearance of surfactant protein A from the lung

Differential effect of surfactant and its saturated phosphatidylcholines on human blood macrophages

A Pneumocyte–Macrophage Paracrine Lipid Axis Drives the Lung toward Fibrosis

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