Tyrosine Kinase Activation in Response to Fungal Spores Is Primarily Dependent on Endogenous Reactive Oxygen Production in Macrophages

Details

• Personal Author:
  Kefalides NA ; Lewis, Daniel M. ; Shahan TA ; Simpson J ; Sorenson WG
• Description:
  Studies from our laboratory (Shahan, T. A., Sorenson, W. G., and Lewis, D. M. (1994) Environ. Res. 67, 98-104) demonstrated that spores from different fungal species differentially activate rat alveolar macrophages as detected by the measurement of superoxide anion and cytokine production (Shahan, T. A., Siegel, P. D., Sorenson, W. G., Kuschner, W. G., and Lewis, D. M. (1998) Am. J. Respir. Cell Mol. Biol. 18, 435-441). Spores from Aspergillus candidus stimulated production of the highest levels of superoxide anion (5.2 nmol/1.0 x 10(6) alveolar macrophages (AMs)/30 min), followed by those from Aspergillus niger (2.4 nmol/1.0 x 10(6) AMs/30 min) and Eurotium amstelodami (0.4 nmol/1.0 x 10(6) AMs/30 min). The mechanism of this differential activation was studied. Our data demonstrate that the tyrosine kinases p56(Hck), p72(Syk), p77(Btk), p62(Yes), p56(Lck), and p59(Fyn) were specifically activated in response to spores from A. candidus, whereas spores from either A. niger or E. amstelodami activated p56(Hck), p72(Syk), and p77(Btk). Kinetic analysis of specific tyrosine kinases demonstrated that p56(Hck), p72(Syk), and p77(Btk) were activated faster and to a greater extent by spores from A. candidus as compared with spores from E. amstelodami. These data suggest a relationship between reactive oxygen species and tyrosine kinase activation. Treatment of AMs with H(2)O(2) (1 mM) caused the activation of p72(Syk) only, whereas treatment with superoxide dismutase and catalase before treatment with the spores had no effect on tyrosine kinase activation. Incubation with NADPH oxidase inhibitors inhibited both superoxide anion production and the activation of p56(Hck), p72(Syk), and p77(Btk) in response to fungal spores. These data indicate that endogenous reactive oxygen species are necessary for the activation of p56(Hck), p72(Syk), and p77(Btk) by spores; they also indicate that some species of spores are capable of activating tyrosine kinases independent of superoxide anion. [Description provided by NIOSH]
• Subjects:
  Animals Fungi Laboratories Microbiology Occupational Health Safety
• Keywords:
  Animal Studies Fungal Infections Laboratory Animals Laboratory Testing Microorganisms
• ISSN:
  0021-9258
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; Pennsylvania ; 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:
  275
• Issue:
  14
• NIOSHTIC Number:
  nn:20020804
• Citation:
  J Biol Chem 2000 Apr; 275(14):10175-10181
• Contact Point Address:
  University of Pennsylvania, Connective Tissue Research Institute, 3624 Market Street, Suite 5-E, Philadelphia, PA 19104-2614
• Email:
  shahan@mail.med.upenn.edu
• CAS Registry Number:
  L-Tyrosine (CAS RN 55520-40-6)
• Federal Fiscal Year:
  2000
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Biological Chemistry
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:dfc4c8e21636275cf5617d3d0f45ec1f71b3b4eb88ba9c397f6f96526146efaf2d5e98d8e06270d34979e7d22e9f756fd2ac0992177a73f6a22bfd3de3e540d9
• Download URL:
  https://stacks.cdc.gov/view/cdc/198469/cdc_198469_DS1.pdf
• File Type:
  [PDF - 310.12 KB ]