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Lung Lining Interaction Determines the Fate of Multi‐Walled Carbon Nanotubes (MWCNTs) in vivo
Author(s) -
Botelho D,
Shaffer M,
Porter A,
Chung KF,
Tetley T,
Zhang J,
Gow A
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.1016.2
Subject(s) - neutrophilia , dipalmitoylphosphatidylcholine , in vivo , chemistry , pulmonary surfactant , lung , phagocytosis , phospholipid , carbon nanotube , biophysics , immunology , biochemistry , nanotechnology , materials science , medicine , biology , phosphatidylcholine , microbiology and biotechnology , membrane
MWCNTs are coated by lipid when incubated with dipalmitoylphosphatidylcholine (DPPC)—the primary component of lung lining fluid (LLF). This lipid coating allows MWCNTs to integrate into the LLF, and to be phagocytized by lung macrophages. We propose that in vivo , the presence of surfactant protein‐D (SP‐D) is needed for clearance of MWCNTs. MWCNTs, functionalized by carboxylation (C) or acid‐etched (A), (30‐50nm OD, 0.5‐2μm length) were instilled at 1.5μg/g body weight into C57Bl/6 or SP‐D ‐/‐ mice. In C57Bl/6, C‐MWCNT induced neutrophilia (120.9 ± 55.9 v 0.2 ± 0.24 x10 3 ) and increased cell count (234 ± 57.6 v 100 ± 35.3 x10 3 ), 1 day post instillation (not seen with A‐MWCNTs). Lung mechanics were unchanged; but there was a decrease in phospholipid (PL) content and an increase in surfactant protein‐B (SP‐B) in the LLF (A‐ & C‐MWCNTs); consistent with lipid‐coating of MWCNTs and consequent phagocytosis. 3 days post instillation, neutrophilia, PL content and SP‐B levels resolved, but there was an increase in SP‐D; without significant change in lung mechanics (A‐ & C‐MWCNTs). In SP‐D ‐/‐ mice, C‐MWCNTs elicited an acute neutrophilic response (63.6 ± 23.4 v 1.4 ± 1.44 x10 3 ). SP‐D ‐/‐ mice displayed increased PL at baseline, but no reduction in response to MWCNT exposure, and no change to lung mechanics. Neutrophilia had resolved at 3 days in SP‐D ‐/‐ , but there was impairment of lung mechanics; especially with A‐MWCNTs. Though lipid coating allows for MWCNTs to be phagocytized, in the absence of SP‐D, MWCNTs are not cleared efficiently (as shown by maintenance of PL levels & the presence of MWCNTs in the LLF at 3 days). Failure to clear MWCNTs appears to increase lung collapse by surfactant dysfunction.