title: Alteration of deposition pattern and pulmonary response as a result of improved dispersion of aspirated single-walled carbon nanotubes in a mouse model.
abstract: Nanoparticles have a fundamental dimension of <100 nm. However, on suspension in media, agglomerates of nanoparticles are the more common structure. This is particularly evident in prior intratracheal instillation or aspiration studies of single-walled carbon nanotubes (SWCNT), in which granulomatous lesions encased by epithelioid macrophages were produced by large agglomerates. In this study, we tested the hypothesis of whether exposure to more dispersed SWCNT structures would alter pulmonary distribution and response. A dispersed preparation of single-walled carbon nanotubes (DSWCNT) with a mean diameter of 0.69 microm was given by pharyngeal aspiration to C57BL/6 mice. Electron microscopy demonstrated a highly dispersed, interstitial distribution of DSWCNT deposits by 1 day postexposure. Deposits were generally <1 microm. Macrophage phagocytosis of DSWCNT was rarely observed at any time point. Lung responses were studied by lavage and morphometry at 1 h, 1 day, 7 day, and 1 mo after a single DSWCNT exposure of 10 microg/mouse. Lung sections and lavage cells demonstrated an early, transient neutrophilic and inflammatory phase that rapidly resolved and was similar to that observed with large agglomerates. No granulomatous lesions or epithelioid macrophages were detected. Morphometric measurement of Sirius red staining was used to assess the connective tissue response. The average thickness of connective tissue in alveolar regions was 0.10 +/- 0.02, 0.09 +/- 0.02, 0.10 +/- 0.01, 0.48 +/- 0.04, and 0.88 +/- 0.19 microm for PBS and 1-h, 1-day, 7-day, and 1-mo postexposure groups, respectively. The results demonstrate that dispersed SWCNT are rapidly incorporated into the alveolar interstitium and that they produce an increase in collagen deposition.
authors.affiliation: Pathology and Physiology Research Branch, Health Effects Laboratory, NIOSH, Morgantown, WV 26505, USA. rmercer@cdc.gov
authors.forename: R R
authors.initials: RR
authors.lastname: Mercer
authors.forename: J
authors.initials: J
authors.lastname: Scabilloni
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: E
authors.initials: E
authors.lastname: Kisin
authors.forename: A R
authors.initials: AR
authors.lastname: Murray
authors.forename: D
authors.initials: D
authors.lastname: Schwegler-Berry
authors.forename: A A
authors.initials: AA
authors.lastname: Shvedova
authors.forename: V
authors.initials: V
authors.lastname: Castranova
mesh_terms: D000818:Animals; D001835:Body Weight; D002244:Carbon / Q000493:pharmacokinetics* / Q000494:pharmacology*; D005740:Gases / Q000378:metabolism; D001239:Inhalation / Q000502:physiology*; D008168:Lung / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D051379:Mice; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D008856:Microscopy, Fluorescence; D023421:Models, Animal; D043942:Nanotubes; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D009929:Organ Size; D011650:Pulmonary Alveoli / Q000033:anatomy & histology; D013499:Surface Properties
chemical_list: D005740:Gases; D002244:Carbon