Calcium Mobilization in Human Airway Epithelial Cells by an Airway Disease-Relevant Extract of Hog-Barn Dust

Details

• Personal Author:
  Dodmane PR ; Romberger DJ ; Schulte NA ; Toews ML
• Description:
  RATIONALE. Workers in swine confinement facilities are susceptible to development of chronic inflammatory lung disease, but the active components in the dust and the cellular and molecular mechanisms involved in the disease remain poorly defined. An aqueous hog-barn dust extract (HDE) stimulates release of cytokines IL6 and IL8 from cultured BEAS-2B human airway epithelial cells. Because this response involves activation of the Ca2+-dependent protein kinase C-alpha isozyme, we hypothesized that HDE would stimulate Ca2+ mobilization in these cells also. METHODS. HDE was subjected to gel filtration to separate its components by size, and HDE or fractions were treated with proteinase K to hydrolyze protein components. Intracellular Ca2+ mobilization in confluent BEAS-2B cells was monitored fluorometrically with a Flex Station Ca2+-monitoring system. RESULTS. HDE caused a concentration-dependent increase in Ca2+ mobilization that was comparable to that induced by 10 microM lysophosphatidic acid, with half-maximal effects at 0.7% HDE. Gel filtration of HDE on Sephadex G-100 showed two distinct peaks of Ca2+-mobilizing activity, one with relatively low activity in approximately30-50 kDa MW fractions and a broad peak of strong activity in the very low MW fractions eluting near the end of the run. These Ca2+-mobilizing peaks overlapped with two of the three peaks of IL6- and IL8-releasing activity of HDE identified in separate studies. HDE-induced stimulation of IL6 and IL8 release is reduced but not eliminated by proteinase K treatment of HDE; the larger MW Ca2+-mobilizing activity was also sensitive to proteinase K, but the low MW activity was not. Complete HDE stimulates rapid phosphorylation of EGF receptors but the Ca2+ -mobilizing fractions did not. The higher MW peak exhibited very slow Ca2+ elevation (1-2 min) whereas the low MW peak exhibited rapid Ca2+ elevation (2-10 sec), suggesting different mechanisms for these two components. CONCLUSIONS. These data add Ca2+ mobilization to the signaling mechanisms activated by HDE, consistent with the involvement of protein kinase C-alpha in HDE responses. Multiple Ca2+-mobilizing factors are present in HDE and mediate their Ca2+ responses by different mechanisms. These Ca2+-mobilizing factors likely contribute to the cytokine responses to HDE in isolated cells and to dust-induced lung disease in hog-barn workers. [Description provided by NIOSH]
• Subjects:
  Agriculture Air Pollutants, Occupational Communicable Diseases Confined Spaces Disinfectants Dust Environmental Monitoring Irritants Laboratories Lung Lung Diseases Occupational Diseases Occupational Exposure Occupational Health Particulate Matter Respiratory Function Tests Respiratory Hypersensitivity Respiratory System Respiratory Tract Diseases Risk Assessment Risk Factors Safety Workplace

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• Keywords:
  Agricultural-industry Agricultural-processes Agricultural-workers Air-sampling Air-sampling-techniques Air-treatment-equipment Airborne-particles Breathing Confined-spaces Diseases Dust-exposure Dust-inhalation Dust-measurement Dust-particles Exposure-assessment Exposure-levels Exposure-methods Infection-control Infectious-diseases Laboratory-techniques Lung-cells Lung-disease Lung-disorders Lung-function Lung-irritants Occupational-diseases Occupational-exposure Occupational-hazards Occupational-health Occupational-respiratory-disease Particle-aerodynamics Particulate-dust Pulmonary-clearance Pulmonary-congestion Pulmonary-disorders Pulmonary-function Pulmonary-function-tests Pulmonary-system Pulmonary-system-disorders Respirable-dust Respiration Respiratory-hypersensitivity Respiratory-infections Respiratory-irritants Respiratory-system-disorders Risk-analysis Risk-factors Statistical-analysis Work-analysis Work-areas Work-environment Work-operations Work-performance Work-practices Worker-health Workplace-studies

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• ISSN:
  1073-449X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  Louisiana ; Nebraska ; OSHA Region 6 ; OSHA Region 7
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  181
• NIOSHTIC Number:
  nn:20037073
• Citation:
  Am J Respir Crit Care Med 2010 May; 181(Meeting Abstracts):A6379
• Email:
  mtoews@unmc.edu
• Federal Fiscal Year:
  2010
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center, Omaha, Nebraska
• Peer Reviewed:
  False
• Start Date:
  20060801
• Source Full Name:
  American Journal of Respiratory and Critical Care Medicine
• Supplement:
  Meeting Abstracts
• End Date:
  20160731
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:ec597fa986d3bd59c6b18e724513945878fafca86ad40133377ea3b025c07c0e26aa1f2eaf2670f47775419b833bc6faf90668ee035bf77e9a3490f5e551efbd
• Download URL:
  https://stacks.cdc.gov/view/cdc/188230/cdc_188230_DS1.pdf
• File Type:
  [PDF - 18.12 KB ]