Comparative Assessment of In Vitro Toxicity Induced by Crystalline Silica and Multiwalled Carbon Nanotubes in Human and Mouse Macrophages

Details

• Personal Author:
  Mustafa GM
• Description:
  Pulmonary exposure to particles like crystalline silica (CS) and multi-walled carbon nanotubes (MWCNTs) are known occupational hazards. Once in the lung, these particles activate alveolar macrophages (AM), a first step in the complicated inflammatory cascade and development of diseases. To study the mechanisms involved in particle induced inflammation at the cellular level, human (THP-1) and mouse (RAW 264.7) macrophages were used as in vitro models and toxicity of CS and MWCNTs was tested. Cytotoxic dose-responses of each particle were determined at final concentrations of 0.9, 1.8, 3.7, 7.5, 15, 30, 60, 120, 240 and 480 microg/cm2 for 24-hrs. Both particles caused a dose-dependent reduction in cell viability. Four concentrations pertaining to 0%, 10%, 30% and 60% toxicity for each cell and particle type were chosen for cytokine analysis: 41 markers in THP-1 and 32 markers in RAW 264.7 were measured. Activation of inflammasome cascade (IL18), pro-inflammatory markers (TNF-alpha), dysregulation (IL6) and fibrotic markers like growth factors, some of which play an important role in fibrosis, were observed. Cytokines involved in inflammation (IL1-B, IL18) and cell recruitment (MCP- 1, MIP) were found to be elevated. Based on TH1/TH2 (IL18/IL4) ratio, there was a concentration-dependent polarization to TH1 response. Overall, THP-1 cells produced a greater inflammatory response to particle exposure than RAW 264.7 cells and MWCNTs were more potent than CS. Data clustering showed MWCNTs and CS treated THP-1 and RAW cells had 24 and 7 common cytokines, respectively, and 11 cytokines were found to be common between both cell lines and particle types. Principle component analysis showed that the response, at same doses can be easily distinguished between particle type and was more apparent in THP-1 than RAW cells. In conclusion, both particle exposures resulted in significant cytotoxicity as well as production of inflammatory mediator in a concentration-dependent manner. However, THP -1 cells were more responsive than RAW cells and the potency of MWCNTs observed was much higher compared to silica at equal mass in both cell types, possibly due to difference in particle size and also due to difference in ASC inflammasome/casp1 activation cascade between two cell types. Ongoing transcriptomic studies may further differentiate the mechanisms of particle toxicity in different types of macrophages. [Description provided by NIOSH]
• Subjects:
  Biomarkers Blood Cytotoxins Environmental Exposure Growth Immune System Laboratories Lung Macrophages Occupational Health Particulate Matter Respiratory System Safety Silicon Dioxide Toxicology

  More +
• Keywords:
  Alveolar Cells Carbon Nanotubes Cell Type Cellular Effects Cellular Reactions CNT Crystalline Silica Cytokines Cytotoxic Effects Cytotoxicity Dose Response Exposure Assessment Exposure Levels Growth Factors Humans Immune Reaction Immune System In Vitro Study Laboratory Animals Laboratory Testing Lung Cells Multi-walled Carbon Nanotubes MWCNT Nanotechnology Nanotoxicology Nanotubes Particle Size Pulmonary Effects

  More +
• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  California ; OSHA Region 3 ; OSHA Region 9 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  42
• Volume:
  174
• Issue:
  1
• NIOSHTIC Number:
  nn:20058855
• Citation:
  Toxicologist 2020 Mar; 174(1):42
• CAS Registry Number:
  Carbon nanotubes (CAS RN 308068-56-6) ; Quartz (SiO2) (CAS RN 14808-60-7)
• Federal Fiscal Year:
  2020
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 59th Annual Meeting and ToxExpo, March 15-19, 2020, Anaheim, California
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:4094a01cf24aa0b27adcceec7adf85e55055945c03e36970fd0aaa753caf9cf67c8bf8e6c156c83079f7877ce2361004e917b57d9b2620b008467ae46bdd3982
• Download URL:
  https://stacks.cdc.gov/view/cdc/223240/cdc_223240_DS1.pdf
• File Type:
  [PDF - 523.32 KB ]