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. 1994 Dec;102(Suppl 10):69–74. doi: 10.1289/ehp.94102s1069

Mechanisms associated with human alveolar macrophage stimulation by particulates.

A Holian 1, K Kelley 1, R F Hamilton Jr 1
PMCID: PMC1566985  PMID: 7705310

Abstract

Asbestos and silica are well-known fibrogenic dusts. However, there is no comprehensive understanding of the molecular and cellular events that lead to fibrosis as a consequence of asbestos or silica inhalation. Previous studies have shown that asbestos stimulates superoxide anion production in alveolar macrophages through the phospholipase C/protein kinase C pathway. In contrast, silica does not appear to activate this pathway nor stimulate superoxide anion production, but silica does stimulate cytokine release by some undetermined pathway. Therefore, using human alveolar macrophages isolated from normal healthy volunteers, we evaluated the potential involvement of intracellular calcium and tyrosine kinases as potential signal transduction pathways. In the absence of serum, crystalline silica, and to a lesser extent amorphous silica, caused a rapid and dose-dependent elevation of intracellular calcium coming from the extracellular space. However, in the presence of serum, which is required for silica-stimulated cytokine release, neither form of silica caused noticeable elevation of intracellular calcium. Silica, however, did increase the extent of tyrosine phosphorylation, most notably of proteins at approximately 46 and 50 kDa, suggesting activation of a tyrosine kinase pathway. Preincubation of alveolar macrophages for 24 hr with silica-primed human alveolar macrophages for enhanced interleukin-1 beta (IL-1 beta) release stimulated by endotoxin (LPS) that was dose dependent. The enhanced LPS-stimulated release of IL-1 beta correlated with enhanced mitogen-activated protein kinase activity. Taken together, these results indicate that a tyrosine kinase pathway is activated during silica stimulation of human alveolar macrophages.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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