Involvement of protein kinase C, phospholipase C, and protein tyrosine kinase pathways in oxygen radical generation by asbestos-stimulated alveolar macrophage.

Abstract

Although asbestos stimulates oxygen radical generation in alveolar macrophages, the exact mechanism is still not clear. The purpose of this study was to compare the ability of three asbestos fibers (amosite, chrysotile, and crocidolite) to generate oxygen radicals in macrophages and examine the mechanism of this action. All asbestos fibers were able to induce chemiluminescence but chrysotile induced maximal chemiluminescence at higher concentrations than amosite and crocidolite. Protein kinase C (PKC) inhibitors (sphingosine and staurosporine) suppressed the ability of asbestos to induce oxygen radical generation. Phospholipase C (PLC) inhibitors (U73122 and neomycin) and protein tyrosine kinase (PTK) inhibitors (erbstatin and genistein) decreased oxygen radical generation of asbestos-stimulated alveolar macrophages. Oxygen radical generation was not suppressed by an adenylate cyclase activator (forskolin), a protein kinase A inhibitor (H-8), and a protein serine-threonine phosphatase inhibitor (okadaic acid). PLC and PTK inhibitors suppressed the increment of phosphoinositide turnover by amosite. These results suggest that asbestos fibers induce the generation of oxygen radicals through PTK, PLC, and PKC pathways in a dose-response pattern.

Changes in low molecular weight DNA fragmentation in white blood cells of workers highly exposed to asbestos

“…These observations indicate that H 2 O 2 provides initiating signals for both apoptosis and necrosis, although the time courses for apoptosis and necrosis were dierent (Sakamoto et al 1996). The results of Lim et al (1997) suggest that asbestos ®bres induce the generation of oxygen radicals through protein kinase C, protein tyrosine kinase and phospholipase C pathways in a dose-response pattern.…”

Meconium Inhibits Phagocytosis and Stimulates Respiratory Burst in Alveolar Macrophages

“…Oxidative injury resulting from AM stimulation is a component of the pathophysiology of several respiratory diseases (6,7) and may also be important in MAS. Exposure of AMs to various types of particulates, including bacteria such as Staphylococcus aureus (26) and Pneumocystis carinii (27), and other particles, including zymosan (28), asbestos fibers (29), and various environmental air pollution particles (30), have been shown to stimulate a respiratory burst response and production of ROS. However, the magnitude and the duration of the oxidative response after ingestion of particles is variable and may in part depend on the specific receptors that are ligated.…”

Mechanism of refractory ceramic fiber- and rock wool-induced cytotoxicity in alveolar macrophages

“…were used as AM sources. The AMs were obtained from the bronchoalveolar lavage cells as previously described (Lim et al 1997). Brie¯y, the rats were anesthetized with sodium pentobarbital (60 mg/kg, intraperitoneally).…”