Carbon nanotubes induce immune suppression via direct effects on dendritic cells

Details

• Personal Author:
  Fadeel B ; Kagan VE ; Kisin ER ; Murray AR ; Shurin GV ; Shurin MR ; Shvedova AA ; Star A ; Tkach A ; Young SH
• Description:
  Mounting evidence indicates that exposure to nanoparticles (NP) is able to modify immune responses. However, cellular and molecular mechanisms of immune responses elicited by NP are poorly understood. In the current study, we evaluated site-specific pulmonary inflammation and systemic immune response in mice after pulmonary exposure to single walled carbon nanotubes (SWCNT). SWCNT exposure caused inflammation, pulmonary damage and an altered cytokine network in the lung. SWCNT-induced inflammation facilitated the recruitment of dendritic cells (DC) to the lung tissues, increasing chances of direct DC/SWCNT interactions. Local inflammatory response in vivo was accompanied by modified systemic immunity as documented by decreased proliferation of splenic T cells. To assess if DC could be responsible for modulation of systemic immunity in SWCNT-treated mice, we evaluated the ability of SWCNT-exposed DC to alter T cell responses in vitro. Here we demonstrate that co-culturing of T cells with SWCNT- exposed DC suppressed the T cell proliferation response upon re-stimulation with freshly generated, unexposed DC. Further, exposure of DC to SWCNT did not alter DC phenotype. Exposure of DC to E. coli LPS induced phenotypical maturation of DC. When LPS-exposed DC were mixed with T cells we observed facilitated T cell proliferation. Administration of LPS + SWCNT to DC did not change LPS-induced DC phenotypical maturation. Indeed, when T cells were mixed with LPS+SWCNT treated DC we observed decreased proliferation. Combined, these findings suggest that SWCNT do not interfere with recognition of LPS by DC. We can speculate that SWCNT exposure may intervene with antigen capture/processing and/or presentation, thereby leading to compromised DC/T cell interactions. Overall, our data suggest that exposure to SWCNT modifies systemic immunity by modulating DC function. [Description provided by NIOSH]
• Subjects:
  Cytotoxins Hazardous Substances Immune System Laboratories Lung Occupational Health Respiratory System Safety
• Keywords:
  Cell-damage Cell-function Cellular-reactions Cytotoxic-effects Health-hazards Immune-reaction Immune-system In-vivo-study Laboratory-animals Laboratory-testing Lung-cells Lung-function Lung-tissue Molecular-biology Nanotechnology Pulmonary-function Pulmonary-system

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• ISSN:
  1096-6080
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; OSHA Region 3 ; OSHA Region 9 ; Pennsylvania ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  126
• NIOSHTIC Number:
  nn:20040531
• Citation:
  Toxicologist 2012 Mar; 126(Suppl 1):276
• CAS Registry Number:
  Carbon (CAS RN 7440-44-0)
• Federal Fiscal Year:
  2012
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of Pittsburgh at Pittsburgh
• Peer Reviewed:
  False
• Start Date:
  20050701
• Source Full Name:
  The Toxicologist. Society of Toxicology 51st Annual Meeting and ToxExpo, March 11-15, 2012, San Francisco, California
• Supplement:
  1
• End Date:
  20160630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e67d4c0207e196039b2ee8b89acb63d601bbea371603565e0f64142c4f366750fae1bbf6236d0f6cd34515a8d847b064cc64c8caae092dfe034d18b443db544e
• Download URL:
  https://stacks.cdc.gov/view/cdc/193348/cdc_193348_DS1.pdf
• File Type:
  [PDF - 474.56 KB ]