Mechanistic Links Between the Lung and the Systemic Microcirculation After Nanoparticle Exposure

Details

• Personal Author:
  Castranova, Vincent ; Chen B ; Donlin M ; Frazer D ; Frisbee J ; Goodwill A ; Hubbs A ; Nurkiewicz TR
• Description:
  Previous studies in our laboratory have shown that pulmonary nanoparticle exposure causes peripheral microvascular dysfunction. This dysfunction is characterized by impaired endothelium-dependent arteriolar dilation and venular leukocyte adhesion. The mechanisms that produce these effects remain poorly understood. The purpose of this study was to determine if neurological mechanisms and/or circulating leukocytes play a fundamental role between pulmonary exposure and peripheral microvascular dysfunction. Rats were exposed to TiO2 nanoparticles via inhalation (primary particle diameter approximately 21 nm) at depositions of 4-90 ug/rat. Some rats received a bolus dose of cyclophosphamide (200 ug/g, i.p.) 3 days prior to nanoparticle exposure to deplete circulating neutrophils. The spinotrapezius muscle was prepared for intravital microscopy 24 hrs after exposures. Intraluminal infusion of the Ca2+ ionophore A23187 (10-7 M, pipette concentration) was used to evaluate endothelium- dependent arteriolar dilation. Histological sections of the spinotrapezius muscle and lung were prepared, and plasma was sampled from each rat for multiplex analyses. Following nanoparticle exposure, plasma IL-1, 2, 13 and ICAM-1 were altered. Consistent with previous experiments, nanoparticle exposure significantly limited arteriolar dilation (in response to A23187) to 0-7% of the normal maximum response. Co-incubation with the fast Na+ channel antagonist tetrodotoxin (TTX, 10-6 M) restored dilation by as much as 54%. Neutrophil depletion similarly resored dilation by as much as 42%. These mechanistic data support prominent hypotheses that suggest peripheral vascular effects associated with particle exposure are due to neurogenic and/or inflammatory mechanisms. [Description provided by NIOSH]
• Subjects:
  Biological Factors Blood Environmental Monitoring Hematologic Tests Irritants Laboratories Lung Lung Diseases Microbiology Musculoskeletal System Occupational Health Particulate Matter Respiratory Function Tests Respiratory Hypersensitivity Respiratory System Respiratory Tract Diseases Safety

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• Keywords:
  Biological-effects Biological-factors Blood-analysis Blood-plasma Blood-vessels Dose-response Exposure-assessment Exposure-levels Exposure-methods Inhalation-studies Laboratory-animals Lung-disorders Lung-function Lung-irritants Microscopic-analysis Microscopy Musculoskeletal-system Nanotechnology Particle-aerodynamics Particulate-dust Particulates Pulmonary-disorders Pulmonary-function-tests Pulmonary-system-disorders Respiratory-hypersensitivity Respiratory-irritants Respiratory-system-disorders Statistical-analysis

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  OSHA Region 3 ; 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:
  108
• Issue:
  1
• NIOSHTIC Number:
  nn:20035261
• Citation:
  Toxicologist 2009 Mar; 108(1):279
• Federal Fiscal Year:
  2009
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 48th Annual Meeting and ToxExpo, March 15-19, 2009, Baltimore, Maryland
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:f89e904220b2d1736aaebd801d9f7a4aacf2aeee1bd8cca1603b90f241c5ae926a5f41d2c0f26e5229c8f66ac5a27dde17766725bcc3f03eae6ddba59a2702f9
• Download URL:
  https://stacks.cdc.gov/view/cdc/187176/cdc_187176_DS1.pdf
• File Type:
  [PDF - 1.58 MB ]