Role of αvβ5 integrin receptor in endocytosis of crocidolite and its effect on intracellular glutathione levels in human lung epithelial (A549) cells

Pande, Priyadarshini; Mosleh, Tariq; Aust, Ann E.

doi:10.1016/j.taap.2005.07.017

Cited by 28 publications

(26 citation statements)

References 23 publications

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“…We observed the largest amount of crocidolite uptake in mesothelial cells under serum-free conditions; this result was in contrast to those of previous reports using pulmonary epithelial cells 25,33 and macrophages. 34,35 We believe that the difference in the speed at which crocidolite fibers sink had influenced the results, although the depth of the medium during incubation was only o0.2 cm (6-cm dish with 4 ml of medium).…”

Section: Discussioncontrasting

confidence: 99%

“…Supporting this idea, the nonprofessional phagocytic system of asbestos is not specific to mesothelial cells. 13,25 The transferrin receptor protein is an integral membrane protein that mediates the uptake of transferrin-iron complexes, and TFRC is considered the major protein responsible for iron uptake. 50 TFRC is known to be involved in clathrinmediated endocytosis, which is a form of endocytosis different from phagocytosis.…”

Section: Discussionmentioning

confidence: 99%

“…21,22 We showed that the mesothelial endocytosis of crocidolite was accompanied by F-actin and Rab5a assembly. 23 Reportedly, fiber internalization increased once the fiber was coated with vitronectin, and integrin avb5 was suggested to be a receptor for vitronectin-coated crocidolite 24,25 and chrysotile. 26 However, even in those studies, a significant amount of asbestos fibers entered the cells in the absence of serum.…”

mentioning

confidence: 99%

“…25 The asbestos surface is well known to adsorb proteins. [27][28][29] Therefore, we hypothesized that asbestos fibers without a protein coating may bind to the receptor proteins on the mesothelial cell surface.…”

mentioning

confidence: 99%

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Receptor role of the annexin A2 in the mesothelial endocytosis of crocidolite fibers

Yamashita

Nagai

Toyokuni

2015

Laboratory Investigation

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Asbestos-induced mesothelioma is a worldwide problem. Parietal mesothelial cells internalize asbestos fibers that traverse the entire lung parenchyma, an action that is linked to mesothelial carcinogenesis. Thus far, vitronectin purified from serum reportedly enhances the internalization of crocidolite by mesothelial cells via integrin avb5. To reveal another mechanism by which mesothelial cells endocytose (phagocytose) asbestos, we first evaluated the effects of serum on asbestos uptake, which proved to be nonessential. Thereafter, we undertook a study to identify proteins on the surface of mesothelial cells (MeT5A) that act as receptors for asbestos uptake based on the assumption that receptors bind to asbestos with physical affinity. To this end, we incubated the membrane fraction of MeT5A cells with crocidolite or chrysotile and evaluated the adsorbed proteins using sodium dodecyl sulfate polyacrylamide gel analysis. Next, we extensively identified the proteins using an in-solution or in-gel digestion coupled with mass spectrometry. Among the identified proteins, annexin A2 (ANXA2) and transferrin receptor protein 1 (TFRC) were distinguished because of their high score and presence at the cell surface. Crocidolite uptake by MeT5A cells was significantly decreased by shRNA (short hairpin RNA)-induced knockdown of ANXA2 and direct blockade of cell surface ANXA2 using anti-ANXA2 antibody. In addition, abundant ANXA2 protein was present on the cell membrane of mesothelial cells, particularly facing the somatic cavity. These findings demonstrate that ANXA2 has a role in the mesothelial phagocytosis of crocidolite and may serve as its receptor.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Receptor role of the annexin A2 in the mesothelial endocytosis of crocidolite fibers

Yamashita

Nagai

Toyokuni

2015

Laboratory Investigation

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“…Adsorption of vitronectin, a serum protein, onto the asbestos surface (chrysotile and crocidolite) was reported to enhance asbestos internalization by mesothelial and epithelial cells via the integrin alphaVbeta5 signaling pathways. (28)(29)(30) Following the internalization of asbestos fibers into mesothelial cells, we have observed in the previous study that the asbestos fibers were surrounded by the small GTPase, Rab5a, which is a marker of the early endosome and phagosome. (17,31) Considering that the size of an endosome can be up to 1 lm, (32,33) asbestos fibers that are larger than a few microns could be internalized by a phagocytosislike mechanism rather than that of the endosome.…”

Section: Asbestos Fibers Are Endocytosed By Mesothelial and Epitheliamentioning

confidence: 99%

Differences and similarities between carbon nanotubes and asbestos fibers during mesothelial carcinogenesis: Shedding light on fiber entry mechanism

Nagai

Toyokuni

2012

Cancer Science

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The emergence of nanotechnology represents an important milestone, as it opens the way to a broad spectrum of applications for nanomaterials in the fields of engineering, industry and medicine. One example of nanomaterials that have the potential for widespread use is carbon nanotubes, which have a tubular structure made of graphene sheets. However, there have been concerns that they may pose a potential health risk due to their similarities to asbestos, namely their high biopersistence and needle‐like structure. We recently found that despite these similarities, carbon nanotubes and asbestos differ in certain aspects, such as their mechanism of entry into mesothelial cells. In the study, we showed that non‐functionalized, multi‐walled carbon nanotubes enter mesothelial cells by directly piercing through the cell membrane in a diameter‐ and rigidity‐dependent manner, whereas asbestos mainly enters these cells through the process of endocytosis, which is independent of fiber diameter. In this review, we discuss the key differences, as well as similarities, between asbestos fibers and carbon nanotubes. We also summarize previous reports regarding the mechanism of carbon nanotube entry into non‐phagocytic cells. As the entry of fibers into mesothelial cells is a crucial step in mesothelial carcinogenesis, we believe that a comprehensive study on the differences by which carbon nanotubes and asbestos fibers enter into non‐phagocytic cells will provide important clues for the safer manufacture of carbon nanotubes through strict regulation on fiber characteristics, such as diameter, surface properties, length and rigidity. (Cancer Sci, doi: 10.1111/j.1349‐7006.2012.02326.x, 2012)

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Faserstäube, anorganisch [MAK Value Documentation in German language, 2018]

Hartwig

Arand²

2018

The MAK‐Collection for Occupational Health and Safety

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The German Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area has reevaluated the general aspects of the toxicity of inorganic fibrous dusts. As a first step a documentation on the effects caused by inhalation of inorganic fibrous dusts and the mode of action for their toxicity was set up. For the elucidation of the mechanism of the toxicity and carcinogenicity of fibers, data derived from studies with asbestos fibers were also considered, in order to obtain some knowledge with regard to the biological effects of the other inorganic fibrous dusts. The formation of tumors in the lungs and on serous membranes is mainly the result of inflammatory processes. Chronic inflammation and cell proliferation are caused by the impairment of fiber clearance, whereby inflammation‐promoting cytokines, growth factors, reactive oxygen (ROS) and nitrogen species (RNS) and chlorine radicals are released from the macrophages, inflammatory cells, alveolar cells and mesothelial cells. The generation of these radicals leads to genotoxic effects. In addition intracellular formation of ROS and RNS can be caused by the fibers themselves, as a result of their own surface reactivity. Fibers can stimulate cell receptors and inflammasomes. Each fiber dust group will be evaluated individually and, depending on the data available, may be classified in one of the categories for carcinogens. The Commission has already begun this procedure.

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Role of αvβ5 integrin receptor in endocytosis of crocidolite and its effect on intracellular glutathione levels in human lung epithelial (A549) cells

Cited by 28 publications

References 23 publications

Receptor role of the annexin A2 in the mesothelial endocytosis of crocidolite fibers

Receptor role of the annexin A2 in the mesothelial endocytosis of crocidolite fibers

Differences and similarities between carbon nanotubes and asbestos fibers during mesothelial carcinogenesis: Shedding light on fiber entry mechanism

Faserstäube, anorganisch [MAK Value Documentation in German language, 2018]

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