Silicosis and fibrogenesis: Fact and artifact

Abstract

Although the pulmonary and extrapulmonary manifestations of silicosis in humans have been extensively documented, the mechanisms by which the fibrogenic effects of silica are manifested remain obscure. In this review, both in vitro and in vivo models of silicosis are discussed, with emphasis on the potential methodological pitfalls of each. In animal models, for example, species variability, silica type and route of administration all effect the results obtained. Tissue culture work has provided evidence that the fibroblast-macrophage interaction is a key event in fibrogenesis. However, critical variables in experimental design make it difficult to compare the often conflicting results of different workers. Experimental conditions that directly affect collagen chain biosynthesis and subsequent hydroxylation of proline appear to be of particular importance. It is concluded that, in part because of methodological difficulties, there are insufficient data to draw firm conclusions regarding the effect of silica-exposed macrophages on collagen biosynthesis by fibroblasts in vitro; there are few, if any, data concerning the role of the macrophage that has ingested silica in human or animal models of silicosis.

Potentiation of Butylated Hydroxytoluene-induced Acute Lung Damage by Oxygen

“…From our data it is tempting to speculate about the role of the macrophage: what signal turns on the macrophages in this model and are they involved in the subsequent prohferation of the "interstitiar cells? Is there a "fibrogenic factor" being secreted analogous to that proposed in siHcosis (20)? There is no obvious event, such as is known to occur in silicosis, in which macrophages ingest sihca particles, lyse, and thereby exert their effects (20).…”

“…Is there a "fibrogenic factor" being secreted analogous to that proposed in siHcosis (20)? There is no obvious event, such as is known to occur in silicosis, in which macrophages ingest sihca particles, lyse, and thereby exert their effects (20).…”

Potentiation of Butylated Hydroxytoluene-induced Acute Lung Damage by Oxygen

“…From our data it is tempting to speculate about the role of the macrophage: what signal turns on the macrophages in this model and are they involved in the subsequent prohferation of the "interstitiar cells? Is there a "fibrogenic factor" being secreted analogous to that proposed in siHcosis (20)? There is no obvious event, such as is known to occur in silicosis, in which macrophages ingest sihca particles, lyse, and thereby exert their effects (20).…”

“…Is there a "fibrogenic factor" being secreted analogous to that proposed in siHcosis (20)? There is no obvious event, such as is known to occur in silicosis, in which macrophages ingest sihca particles, lyse, and thereby exert their effects (20).…”

Silica associated mixed connective tissue disorder in a stone crusher

“…Silica exposure has been implicated as a possible cause. [3] Crystalline silica (quartz) particles less than 1 μ are the most pathogenic in silicosis. These particles are phagocytosed by macrophages and are transported to the regional lymph nodes.…”

Essential role of ROS-mediated NFAT activation in TNF-α induction by crystalline silica exposure

“…Crystalline silica is a documented carcinogen, but the molecular and cellular mechanisms involved in silica-induced pathogenesis are not fully understood (2,17,27). In this study, we investigated the possible involvement of NFAT in silicainduced TNF-␣ transcription in mouse Cl41 cells.…”

Potentiation of Butylated Hydroxytoluene-induced Acute Lung Damage by Oxygen

“…From our data it is tempting to speculate about the role of the macrophage: what signal turns on the macrophages in this model and are they involved in the subsequent prohferation of the "interstitiar cells? Is there a "fibrogenic factor" being secreted analogous to that proposed in siHcosis (20)? There is no obvious event, such as is known to occur in silicosis, in which macrophages ingest sihca particles, lyse, and thereby exert their effects (20).…”

“…Is there a "fibrogenic factor" being secreted analogous to that proposed in siHcosis (20)? There is no obvious event, such as is known to occur in silicosis, in which macrophages ingest sihca particles, lyse, and thereby exert their effects (20).…”

Silica associated mixed connective tissue disorder in a stone crusher

“…Silica exposure has been implicated as a possible cause. [3] Crystalline silica (quartz) particles less than 1 μ are the most pathogenic in silicosis. These particles are phagocytosed by macrophages and are transported to the regional lymph nodes.…”

Essential role of ROS-mediated NFAT activation in TNF-α induction by crystalline silica exposure

“…Crystalline silica is a documented carcinogen, but the molecular and cellular mechanisms involved in silica-induced pathogenesis are not fully understood (2,17,27). In this study, we investigated the possible involvement of NFAT in silicainduced TNF-␣ transcription in mouse Cl41 cells.…”

Potentiation of Butylated Hydroxytoluene-induced Acute Lung Damage by Oxygen

“…From our data it is tempting to speculate about the role of the macrophage: what signal turns on the macrophages in this model and are they involved in the subsequent prohferation of the "interstitiar cells? Is there a "fibrogenic factor" being secreted analogous to that proposed in siHcosis (20)? There is no obvious event, such as is known to occur in silicosis, in which macrophages ingest sihca particles, lyse, and thereby exert their effects (20).…”

“…Is there a "fibrogenic factor" being secreted analogous to that proposed in siHcosis (20)? There is no obvious event, such as is known to occur in silicosis, in which macrophages ingest sihca particles, lyse, and thereby exert their effects (20).…”

Silica associated mixed connective tissue disorder in a stone crusher

“…Silica exposure has been implicated as a possible cause. [3] Crystalline silica (quartz) particles less than 1 μ are the most pathogenic in silicosis. These particles are phagocytosed by macrophages and are transported to the regional lymph nodes.…”

Essential role of ROS-mediated NFAT activation in TNF-α induction by crystalline silica exposure

“…Crystalline silica is a documented carcinogen, but the molecular and cellular mechanisms involved in silica-induced pathogenesis are not fully understood (2,17,27). In this study, we investigated the possible involvement of NFAT in silicainduced TNF-␣ transcription in mouse Cl41 cells.…”