title: Pulmonary surfactant coating of multi-walled carbon nanotubes (MWCNTs) influences their oxidative and pro-inflammatory potential in vitro.
abstract: BACKGROUND
  Increasing concern has been expressed regarding the potential adverse health effects that may be associated with human exposure to inhaled multi-walled carbon nanotubes (MWCNTs). Thus it is imperative that an understanding as to the underlying mechanisms and the identification of the key factors involved in adverse effects are gained. In the alveoli, MWCNTs first interact with the pulmonary surfactant. At this interface, proteins and lipids of the pulmonary surfactant bind to MWCNTs, affecting their surface characteristics. Aim of the present study was to investigate if the pre-coating of MWCNTs with pulmonary surfactant has an influence on potential adverse effects, upon both (i) human monocyte derived macrophages (MDM) monocultures, and (ii) a sophisticated in vitro model of the human epithelial airway barrier. Both in vitro systems were exposed to MWCNTs either pre-coated with a porcine pulmonary surfactant (Curosurf) or not. The effect of MWCNTs surface charge was also investigated in terms of amino (-NH2) and carboxyl (-COOH) surface modifications.
  
  
  RESULTS
  Pre-coating of MWCNTs with Curosurf affects their oxidative potential by increasing the reactive oxygen species levels and decreasing intracellular glutathione depletion in MDM as well as decreases the release of Tumour necrosis factor alpha (TNF-α). In addition, an induction of apoptosis was observed after exposure to Curosurf pre-coated MWCNTs. In triple cell-co cultures the release of Interleukin-8 (IL-8) was increased after exposure to Curosurf pre-coated MWCNTs. Effects of the MWCNTs functionalizations were minor in both MDM and triple cell co-cultures.
  
  
  CONCLUSIONS
  The present study clearly indicates that the pre-coating of MWCNTs with pulmonary surfactant more than the functionalization of the tubes is a key factor in determining their ability to cause oxidative stress, cytokine/chemokine release and apoptosis. Thus the coating of nano-objects with pulmonary surfactant should be considered for future lung in vitro risk assessment studies.
authors.affiliation: Adolphe Merkle Institute, University of Fribourg, Marly, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Gasser
authors.forename: Peter
authors.initials: P
authors.lastname: Wick
authors.forename: Martin J D
authors.initials: MJ
authors.lastname: Clift
authors.forename: Fabian
authors.initials: F
authors.lastname: Blank
authors.forename: Liliane
authors.initials: L
authors.lastname: Diener
authors.forename: Bing
authors.initials: B
authors.lastname: Yan
authors.forename: Peter
authors.initials: P
authors.lastname: Gehr
authors.forename: Harald F
authors.initials: HF
authors.lastname: Krug
authors.forename: Barbara
authors.initials: B
authors.lastname: Rothen-Rutishauser
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001688:Biological Products / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000633:toxicity*; D018920:Coculture Techniques; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D010539:Permeability / Q000187:drug effects; D010743:Phospholipids / Q000737:chemistry; D011663:Pulmonary Surfactants / Q000737:chemistry; D017382:Reactive Oxygen Species / Q000378:metabolism; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001688:Biological Products; D020099:Coated Materials, Biocompatible; D016209:Interleukin-8; D037742:Nanotubes, Carbon; D010743:Phospholipids; D011663:Pulmonary Surfactants; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D005978:Glutathione; C068291:poractant alfa