Korean J Occup Environ Med.  1999 Dec;11(4):527-533.

Reactive Oxygen Species Generation of Refractory Ceramic Fiber and Rock Wool-Induced Alveolar Macrophage and Associated Signal Transduction Pathway

Affiliations
  • 1Department of Occupational and Environmental Medicine, St. Mary's Hospital, Koera.
  • 2Department of Pharmacology, College of Medicine, The Catholic University of Korea.
  • 3Korean Industrial Health Association, Pusan Industrial Health Center, Korea.
  • 4Jung Hae Industrial Medical Center, Korea.

Abstract


OBJECTIVES
It is known that the high fibrogenecity of particles is connected with their cytotoxicity for macrophages. Although the molecular mechanism leading to fiber-induced fiber-induced cytotoxicity is still not clear, several mechanism have been suggested. The release of reactive oxygen species (ROS) from activated alveolar macrophages (AM) by dust have been suggested as a possible mechanism of particle-induced cell damage. But the mechanism which man-made vitreous fiber (MMVF) induces the production of ROS in AM is still not clear. In this study, we evaluated the relationship between ROS production and lactate dehydrogenase (LDH) release from alveolar treated with refractory ceramic fiber (RF2) or rock wool (RW1) and signal transduction path-way of ROS production in RF2 or RW1 exposed AM.
METHODS
We investigated LDH release from MMVF-stimulated AM for index of cytotoxicity. To determine what kind of signal transduction pathways are involved in MMVF-stimulated ROS generation, we used some drugs which have an effect on the signal transduction pathway.
RESULTS
RF2 and RW1 induced increase of LDH release with dose-dependent manner with RF2 having greater effect than RW1. There was a dose-dependent increase in the production of ROS by RF2 or RW1. At all level of concentration,. RF2 induced more ROS production than RW1. Inhibitors of PKC (bisindolylmaleimide), PLC (U73122 and neomycine) and PTK (genistein and erbstatin) suppressed RF2 or RW1-induced ROS production.
CONCLUSION
There was significant correlation between LDH release and ROS production from AM treated with RF2 or RW1. RF2 and RW1 induced ROS generation through protein kinase C (PKC), phospholipase C (PLC) and protein tyrosin kinase (PTK) pathways.

Keyword

MMVF; Signal transduction pathway; Reactive oxygen species (ROS)

MeSH Terms

Ceramics*
Dust
L-Lactate Dehydrogenase
Macrophages
Macrophages, Alveolar*
Phosphotransferases
Protein Kinase C
Reactive Oxygen Species*
Signal Transduction*
Type C Phospholipases
Wool
Ceramics
Dust
L-Lactate Dehydrogenase
Phosphotransferases
Protein Kinase C
Reactive Oxygen Species
Type C Phospholipases
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