Visualization and quantitative analysis of nanoparticles in the respiratory tract by transmission electron microscopy

被引：105

作者：

Mühlfeld C. ^{[1
]}

Rothen-Rutishauser B. ^{[1
]}

Vanhecke D. ^{[1
]}

Blank F. ^{[1
]}

Gehr P. ^{[1
]}

Ochs M. ^{[1
]}

机构：

[1] Institute of Anatomy, University of Bern, CH-3000 Bern 9

来源：

Particle and Fibre Toxicology | / 4卷 / 1期

关键词：

Total Lung Capacity; Immunogold Label; Colloidal Gold Particle; Conventional Transmission Electron Microscopic; Immunogold Particle;

D O I：

10.1186/1743-8977-4-11

中图分类号：

学科分类号：

摘要：

Nanotechnology in its widest sense seeks to exploit the special biophysical and chemical properties of materials at the nanoscale. While the potential technological, diagnostic or therapeutic applications are promising there is a growing body of evidence that the special technological features of nanoparticulate material are associated with biological effects formerly not attributed to the same materials at a larger particle scale. Therefore, studies that address the potential hazards of nanoparticles on biological systems including human health are required. Due to its large surface area the lung is one of the major sites of interaction with inhaled nanoparticles. One of the great challenges of studying particle-lung interactions is the microscopic visualization of nanoparticles within tissues or single cells both in vivo and in vitro. Once a certain type of nanoparticle can be identified unambiguously using microscopic methods it is desirable to quantify the particle distribution within a cell, an organ or the whole organism. Transmission electron microscopy provides an ideal tool to perform qualitative and quantitative analyses of particle-related structural changes of the respiratory tract, to reveal the localization of nanoparticles within tissues and cells and to investigate the 3D nature of nanoparticle-lung interactions. This article provides information onthe applicability, advantages and disadvantages of electron microscopic preparation techniques and several advanced transmission electron microscopic methods including conventional, immuno and energy-filtered electron microscopy as well as electron tomography for the visualization of both model nanoparticles (e.g. polystyrene) and technologically relevant nanoparticles (e.g. titanium dioxide). Furthermore, we highlight possibilities to combine light and electron microscopic techniques in a correlative approach. Finally, we demonstrate a formal quantitative, i.e. stereological approach to analyze the distributions of nanoparticles in tissues and cells. This comprehensive article aims to provide a basis for scientists in nanoparticle research to integrate electron microscopic analyses into their study design and to select the appropriate microscopic strategy. © 2007 Mühlfeld et al; licensee BioMed Central Ltd.

引用

共 152 条

[1]

Gehr P., Bachofen M., Weibel E.R., The normal human lung: Ultrastructure and morphometric estimation of diffusion capacity, Respir Physiol, 32, pp. 121-140, (1978)

[2]

Gil J., Weibel E.R., Extracellular lining of bronchioles after perfusion-fixation of rat lungs for electron microscopy, Anat Rec, 169, pp. 185-199, (1971)

[3]

Gehr P., Schurch S., Berthiaume Y., Im Hof V., Geiser M., Particle retention in airways by surfactant, J Aerosol Med, 3, pp. 27-43, (1990)

[4]

Schurch S., Gehr P., Im Hof V., Geiser M., Green F., Surfactant displaces particles toward the epithelium in airways and alveoli, Respir Physiol, 80, pp. 17-32, (1990)

[5]

Kilburn K.H., A hypothesis for pulmonary clearance and its implications, Am Rev Respir Dis, 98, pp. 449-463, (1968)

[6]

Brain J.D., Lung macrophages: How many kinds are there? What do they do?, Am Rev Respir Dis, 137, pp. 507-509, (1988)

[7]

Lehnert B.E., Pulmonary and thoracic macrophage subpopulations and clearance of particles from the lung, Environ Health Perspect, 97, pp. 17-46, (1992)

[8]

Warheit D.B., Hartsky M.A., Role of alveolar macrophage chemotaxis in pulmonary clearance responses to inhaled particles: Comparisons among rodent species, Microsc Res Tech, 26, pp. 412-422, (1993)

[9]

Godfrey R.W., Human airway epithelial tight junctions, Microsc Res Tech, 38, pp. 488-499, (1997)

[10]

Maina J.N., West J.B., Thin and strong! The bioengineering dilemma in the structural and functional design of the blood-gas barrier, Physiol Rev, 85, pp. 811-844, (2005)

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