The Impact of Airborne Endotoxin Exposure on Rheumatoid Arthritis-Related Joint Damage, Autoantigen Expression, Autoimmunity, and Lung Disease

Details

• Personal Author:
  Ascherman DP ; Bailey KL ; Duryee MJ ; England BR ; Gaurav R ; Hunter CD ; Mikuls TR ; Nelson AJ ; Poole JA ; Romberger DJ ; Shaw BP ; Thiele GM ; Wang D ; Wolfe MG ; Wyatt TA
• Description:
  Airborne biohazards are risk factors in the development and severity of rheumatoid arthritis (RA) and RA-associated lung disease, yet the mechanisms explaining this relationship remain unclear. Lipopolysaccharide (LPS, endotoxin) is a ubiquitous inflammatory agent in numerous environmental and occupational air pollutant settings recognized to induce airway inflammation. Combining repetitive LPS inhalation exposures with the collagen induced arthritis (CIA) model, DBA1/J mice were assigned to either: sham (saline injection/saline inhalation), CIA (CIA/saline), LPS (saline/LPS 100 ng inhalation), or CIA + LPS for 5 weeks. Serum anti-citrullinated (CIT) protein antibody (ACPA) and anti-malondialdehyde-acetaldehyde (MAA) antibodies were strikingly potentiated with co-exposure (CIA + LPS). CIT- and MAA-modified lung proteins were increased with co-exposure and co-localized across treatment groups. Inhaled LPS exacerbated arthritis with CIA + LPS > LPS > CIA versus sham. Periarticular bone loss was demonstrated in CIA and CIA + LPS but not in LPS alone. LPS induced airway inflammation and neutrophil infiltrates were reduced with co-exposure (CIA + LPS). Potentially signaling transition to pro-fibrotic processes, there were increased infiltrates of activated CD11c+CD11b+ macrophages and transitioning CD11c+CD11bint monocyte-macrophage populations with CIA + LPS. Moreover, several lung remodeling proteins including fibronectin and matrix metalloproteinases as well as complement C5a were potentiated with CIA + LPS compared to other treatment groups. IL-33 concentrations in lung homogenates were enhanced with CIA + LPS with IL-33 lung staining driven by LPS. IL-33 expression was also significantly increased in lung tissues from patients with RA-associated lung disease (N = 8) versus controls (N = 7). These findings suggest that patients with RA may be more susceptible to developing interstitial lung disease following airborne biohazard exposures enriched in LPS. [Description provided by NIOSH]
• Subjects:
  Air Pollutants, Occupational Endotoxins Hazardous Substances Immune System Laboratories Lung Diseases Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Air Pollutants Author Keywords: Collagen Induced Arthritis Autoimmune Diseases Biohazards Exposure Assessment IL-33 Immune Reaction Inhalation Interstitial Lung Disease Laboratory Animals Lung Disease Rheumatoid Arthritis Rheumatoid Disorders

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• ISSN:
  1567-5769
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  Nebraska ; OSHA Region 3 ; OSHA Region 7 ; Pennsylvania
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  100
• NIOSHTIC Number:
  nn:20064525
• Citation:
  Int Immunopharmacol 2021 Nov; 100:108069
• Contact Point Address:
  Jill A.Poole, Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA
• Email:
  japoole@unmc.edu
• Federal Fiscal Year:
  2022
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center - Omaha
• Peer Reviewed:
  True
• Start Date:
  20110901
• Source Full Name:
  International Immunopharmacology
• End Date:
  20270831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:236be23f5ce76e8b63f305bb2bd465bfd9c2a3b8534346edfd286de1b41d4358e5c0b56a52cfaad29c619373416af1db05d48dd9f0d9ff29995454008fbe98de
• Download URL:
  https://stacks.cdc.gov/view/cdc/222972/cdc_222972_DS1.pdf
• File Type:
  [PDF - 7.21 MB ]