3,4-Dichloropropionanilide (DCPA) Inhibits T-Cell Activation by Altering the Intracellular Calcium Concentration Following Store Depletion

Details

• Personal Author:
  Barnett JB ; Brundage KM ; Brundage RA ; Lewis TL
• Description:
  Stimulation of T cells through the T-cell receptor results in the activation of a series of signaling pathways that leads to the secretion of interleukin (IL)-2 and cell proliferation. Influx of calcium (Ca2+) from the extracellular environment, following internal Ca2+ store depletion, provides the elevated and sustained intracellular calcium concentration ([Ca2+](i)) critical for optimal T-cell activation. Our laboratory has documented that exposure to the herbicide 3,4-dichloropropionanilide (DCPA) inhibits intracellular signaling events that have one or more Ca2+ dependent steps. Herein we report that DCPA attenuates the normal elevated and sustained [Ca2+](i) that follows internal store depletion in the human leukemic Jurkat T cell line and primary mouse T cells. DCPA did not alter the depletion of internal Ca2+ stores when stimulated by anti-CD3 or thapsigargin demonstrating that early inositol 1,4,5-triphosphate-mediated signaling and depletion of Ca2+ stores were unaffected. 2-Aminoethyldiphenol borate (2-APB) is known to alter the store-operated Ca2+ (SOC) influx that follows Ca2+ store depletion. Exposure of Jurkat cells to either DCPA or 50 mu M 2-APB attenuated the increase in [Ca2+](i) following thapsigargin or anti-CD3 induced store depletion in a similar manner. At low concentrations, 2-APB enhances SOC influx but this enhancement is abrogated in the presence of DCPA. This alteration in [Ca2+](i), when exposed to DCPA, significantly reduces nuclear levels of nuclear factor of activated T cells (NFAT) and IL-2 secretion. The plasma membrane polarization profile is not altered by DCPA exposure. Taken together, these data indicate that DCPA inhibits T-cell activation by altering Ca2+ homeostasis following store depletion. [Description provided by NIOSH]
• Subjects:
  Animals Herbicides Immune System Laboratories Liver Occupational Health Safety
• Keywords:
  Animal-studies Cell-biology Cell-differentiation Cell-function Cell-metabolism Cell-transformation Cellular-reactions Cellular-transport-mechanism Hepatotoxicity Histopathology Immune-reaction Immune-system Immune-system-disorders Immunotoxins Laboratory-animals

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Nevada ; OSHA Region 3 ; OSHA Region 4 ; OSHA Region 9 ; South Carolina ; 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:
  97-107
• Volume:
  103
• Issue:
  1
• NIOSHTIC Number:
  nn:20034050
• Citation:
  Toxicol Sci 2008 May; 103(1):97-107
• Contact Point Address:
  Rodney A. Brundage, W Virginia Univ, Sch Med, Dept Microbiol Immunol & Cell Biol, POB 9177, Morgantown, WV 26506 USA
• Email:
  jbarnett@hsc.wvu.edu
• Federal Fiscal Year:
  2008
• NORA Priority Area:
  Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
• Peer Reviewed:
  True
• Source Full Name:
  Toxicological Sciences
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:d7ff622604b8394dfe6f5d7a98c469e05c3d14e83b31e07a6d8bb65aefd8b4da293bc5dc29551ab6660cd491e743ee74768aad8a7258a0e6dd3f26ae2c596b6f
• Download URL:
  https://stacks.cdc.gov/view/cdc/189427/cdc_189427_DS1.pdf
• File Type:
  [PDF - 431.10 KB ]