Synergistic Effect of World Trade Center (WTC) Dust Exposure and Chronic Intermittent Hypoxia on Oxidative Stress, Inflammation, and Proliferation

Details

• Personal Author:
  Gow AJ ; Hua J ; Laskin D ; Lee, Stephen A. ; Lehoang O ; Rose P ; Sunderram J ; Sunil V ; Vayas K
• Description:
  Background and Purpose: The collapse of the World Trade Center (WTC) led to a large dust cloud of particles consisting of highly alkaline crushed concrete, gypsum, and synthetic fibers that were inhaled and deposited in the conducting airways. In earlier studies, we reported a 75% prevalence of obstructive sleep apnea (OSA) leading to chronic intermittent hypoxia (CIH) in WTC responders. In rodents, WTC dust exposure leads to upregulation of genes and proteins related to inflammation and oxidative stress, along with abnormal pulmonary structure and function. We hypothesized that CIH due to OSA, in combination with WTC dust exposure, would exacerbate oxidative stress, inflammation, and lung injury. To assess this, we analyzed the effects of CIH following WTC dust exposure on the composition of pulmonary cells and markers of oxidative stress, inflammation, and proliferation. Methods: C57BL/6J mice (male, 6-8 wk) were treated intratracheally with 1 mg WTC dust suspended in 50 µl saline or 50 µl saline control. Mice were then exposed to CIH (90s of hypoxia to reach a nadir oxygen saturation of 5% followed by 90s of re-oxygenation for 8h/day) or room air (19-21% O2) for 5d, 14d, or 28d. The effects of WTC dust and CIH on pulmonary cells were determined by flow cytometry and cytology. Oxidative stress, inflammation, and proliferation markers were evaluated by immunohistochemistry (IHC) for expression of HO-1, CD11b, and PCNA, respectively. Results: Following WTC dust exposure, HO-1 expression significantly increased after 28d (35.2 +/- 13.1 v 14.1 +/- 6.2), while CD11b significantly increased at all post-exposure time points (25.8 +/- 0.6 v 17.0 +/- 4.4 (5d); 11.9 +/- 1.1 v 8.7 +/- 2.0 (14d); 17.0 +/- 1.4 v 12.1 +/- 3.0 (28d)), and PCNA expression significantly increased in the 5d but decreased in the 28d compared to control (7.3 +/- 1.1 v 5.5 +/- 0.6; 17.9 +/- 0.6 v 19.7 +/- 0.5, respectively). CIH caused an increase in expression of HO-1 in both 5d and 28d (37.6 +/- 5.4 v 21.2 +/- 3.1; 30.9 +/- 7.0 v 14.1 +/- 6.2, respectively), an increase in CD11b expression at 14d and 28d (23.8 +/- 2.7 v 8.7 +/- 2.0; 33.3 +/- 2.4 v 12.1 +/- 3.0, respectively), and an increase in PCNA staining at 5d (6.8 +/- 1.0 v 5.5 +/- 0.6). The combination of WTC dust and CIH resulted in a significant increase in neutrophils and lymphocytes at 14d (1.0 +/- 0.5 v 10.8 +/- 3.5; 2.0 +/- 0.6 v 20.6 +/- 4.4, respectively), an increase in HO-1 and CD11b expression at all time points (HO-1: 34.6 +/- 9.4 v 21.2 +/- 3.1 (5d); 94.1 +/- 5.0 v 66.0 +/- 17.1 (14d); 53.4 +/- 15.2 v 14.1 +/- 6.2 (28d)) (CD11b: 26.2 +/- 2.4 v 17.0 +/- 4.4 (5d); 12.7 +/- 1.0 v 8.7 +/- 2.0 (14d); 19.7 +/- 1.4 v 12.1 +/- 3.0 (28d)), and an increase in the percentage of PCNA stained cells at 5d and 28d (7.3 +/- 0.6 v 5.5 +/- 0.6; 23.2 +/- 3.0 v 19.7 +/- 0.5, respectively). There were no observed changes in the phenotype of the cells as determined by flow cytometry. Conclusions: The combination of WTC dust and CIH exacerbates oxidative stress in pulmonary epithelial cells and inflammatory cells. This was associated with upregulation of a pro-fibrotic marker at 5d and 28d, and a heightened immune response at 14d. The two-hit effect of CIH and dust exposure does reveal a novel injury model. [Description provided by NIOSH]
• Subjects:
  Dust Immune System Occupational Health Particulate Matter Safety September 11 Terrorist Attacks
• Keywords:
  Dust Exposure Dust Particles Immune Reaction Oxidative Stress Respirable Dust World Trade Center WTC
• ISSN:
  1096-6080
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Abstract or Summary
• Place as Subject:
  New Jersey ; OSHA Region 2
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  235-236
• Volume:
  198
• NIOSHTIC Number:
  nn:20069320
• Citation:
  Toxicologist 2024 Mar; 198(S1):235-236
• Federal Fiscal Year:
  2024
• Performing Organization:
  RBHS-Robert Wood Johnson Medical School, Piscataway, New Jersey
• Peer Reviewed:
  False
• Start Date:
  20210701
• Source Full Name:
  The Toxicologist. Society of Toxicology 63rd Annual Meeting & ToxExpo, March 10-14, 2024, Salt Lake City, Utah
• End Date:
  20240630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:cbae94ec298f062e8a143b85bd68369ea67934affcd373c26f7d7775ea629ecb81045b32802ba242e2fefc30a1f781ee44792711338d815863d691e31f266e01
• Download URL:
  https://stacks.cdc.gov/view/cdc/207820/cdc_207820_DS1.pdf
• File Type:
  [PDF - 560.58 KB ]