Release of IL-8 from Human Monocytes by Asbestos

It is supposed that neutrophil infiltration into the pulmonary airspace is involved in the pathology of asbestosis development. We investigated interleukin-8(IL-8)release from monocytes by asbestos exposure and a part of the related mechanisms. Chrysotile A asbestos showed the highest stimulating effect among the particulates to which monocytes were exposed, followed by chrysotile B, crocidolite, and SiO2. The optimum concentration of chrysotile A was 50 μg/ml. The amount of IL-8 released was dependent on the incubation time. Leaching magnesium(Mg)from chrysotile A by HCl-treatment signincantly reduced its stimulating effect. Cycloheximide treatment significantly reduced the amount of IL-8 released. The amount of IL-8 released from monocytes was investigated with uncharged, positively or negatively charged dextran to determine the stimulating effect of the surface charges of asbestos. Our results in this investigation showed that the amount of IL-8 release markedly increased when charged dextran was applied. Among the signal transduction inhibitors used in this study, herbimycin A, H-7, calmidazolium, and EGTA reduced the amount of IL-8 released. These results suggest that asbestos stimulates monocytes to release IL-8 synthesized de novo, and that the mechanism of this stimulation is involved in the surface charge of asbestos and Mg contained in chrysotile A. It is also suggested that the signal transduction route in this experiment is associated with cytosolic tyrosine kinase, protein kinase C(PKC), Ca2+, and calmodulin.