Histopathological Changes in Enlarged Thoracic Lymph Nodes during the Development of Silicosis in Rats

Friedetzky, Anke; Garn, Holger; Kirchner, Andrea; Gemsa, Diethard

doi:10.1016/s0171-2985(98)80068-5

Cited by 35 publications

(34 citation statements)

References 7 publications

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“…They also noted enlarged thoracic lymph nodes with immunological abnormalities following silica instillation [112]. The later finding was supported by an earlier study in rats exposed to repeated aerosolized silica, where enlarged lymph nodes were characterized by early T cell infiltration (2 weeks), followed by B cell infiltration (6 weeks) and then finally by macrophages accumulating in granuloma structures surrounded by an even distribution of T and B cells (52 weeks) [113].…”

Section: The Role Of Silica Exposure In Macrophage Immune Dysfunctionmentioning

confidence: 55%

Silica binding and toxicity in alveolar macrophages

Hamilton

Thakur

Holian

2008

Free Radical Biology and Medicine

333

242

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Inhalation of the crystalline form of silica is associated with a variety of pathologies from acute lung inflammation to silicosis, in addition to autoimmune disorders and cancer. Basic science researchers looking at the mechanisms involved with the earliest initiators of disease are focused on how the alveolar macrophage (AM) interacts with the inhaled silica particle and the consequences of silicainduced toxicity on the cellular level. Based on experimental results, several rationales have been developed on exactly how crystalline silica particles are toxic to the macrophage cell that is functionally responsible for clearance of the foreign particle. For example, silica is capable of producing reactive oxygen species (ROS) either directly (on the particle surface) or indirectly (produced by the cell as a response to silica) triggering cell-signaling pathways initiating cytokine release and apoptosis. With murine macrophages, reactive nitrogen species (RNS) are produced in the initial respiratory burst in addition to ROS. An alternative explanation for silica toxicity includes lysosomal permeability, where silica disrupts the normal internalization process leading to cytokine release and cell death. Still other research has focused on the cell surface receptors (collectively known as scavenger receptors) involved in silica binding and internalization. The silica-induced cytokine release and apoptosis is described as the function of receptor-mediated signaling rather than free radical damage. Current research ideas on silica toxicity and binding in the alveolar macrophage are reviewed and discussed.

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Section: The Role Of Silica Exposure In Macrophage Immune Dysfunctionmentioning

confidence: 55%

Silica binding and toxicity in alveolar macrophages

Hamilton

Thakur

Holian

2008

Free Radical Biology and Medicine

333

242

View full text Add to dashboard Cite

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“…NAOTA ET AL. TOXICOLOGIC PATHOLOGY Friedetzky et al (1998) concluded that marked disorganization of thoracic lymph node structures such as granuloma formation and disappearance of B and T lymphocytes may contribute to the immune abnormalities in silicosis patients. Activation of T lymphocytes has been reported in silicosis patients (Otsuki et al 2011;Wu et al 2006).…”

Section: Discussionmentioning

confidence: 99%

Pathological Study of Chronic Pulmonary Toxicity Induced by Intratracheally Instilled Asian Sand Dust (Kosa)

et al. 2012

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Asian sand dust (ASD) events are associated with an increase in pulmonary morbidity and mortality. The number of ASD events has increased rapidly in the east Asian region since 2000. To study the chronic lung toxicity of ASD, saline suspensions of low doses (200 and 400 mg) and high doses (800 and 3,000 mg) of ASD were intratracheally instilled into ICR mice. Animals were sacrificed at 24 hr, 1 week, or 1, 2, or 3 months after instillation. Histopathological examination revealed that ASD induced acute inflammation at 24 hr after instillation. The acute inflammation was transient and subsided at 1 week and 1 month after instillation. At 2 and 3 months after instillation, focal infiltration of lymphocytes with accumulation of epithelioid macrophages, which is a suggestive finding of transformation to granuloma, and granuloma formation were occasionally observed. Aggregation of macrophages containing particles was observed in the pulmonary lymph nodes at 3 months after instillation in high-dose groups. Prolonged inflammatory foci (granuloma) and presence of ASD particles in pulmonary lymph nodes would have a chance to induce immunological modulation leading to adverse health effects in the exposed animals.

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“…3F). Silica particles can be drained by the lymphatic system to the lymph nodes (22). Morphological analysis of lung mediastinal lymph node of silicachallenged animals revealed the presence of silica particles localized inside the lymphoid follicles (Fig.…”

Section: Il-13-pe Treatment Increased the Clearance Of Silica Particlesmentioning

confidence: 96%

IL-13 Immunotoxin Accelerates Resolution of Lung Pathological Changes Triggered by Silica Particles in Mice

Ferreira

Arantes

Nascimento

et al. 2013

The Journal of Immunology

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Instillation of silica into the lungs of rodents results in pathological changes that strongly mimic human silicosis, an occupational lung disease marked by restrictive airway obstruction, inflammation, and fibrosis. Because IL-13 is a pivotal proinflammatory and fibrogenic cytokine, we examined whether a recombinant immunotoxin comprised of human IL-13 and a mutated form of Pseudomonas exotoxin (IL-13–PE) might affect pathological features of experimental silicosis. Mice received a single intranasal instillation of silica particles and were treated with intranasal IL-13–PE every other day from days 21 to 27 postsilica. The sensitivity of putative cell targets to IL-13–PE was also assessed in in vitro settings. Upregulation of IL-13, its receptor subunits IL-13Rα1 and IL-13Rα2, and shared receptor IL-4Rα were associated with development of granulomatous lung inflammation triggered by silica. IL-13–PE inhibited silica-induced granuloma and fibrotic responses noted at 24 h and 15 d after the last treatment. Upregulation of TNF-α, TGF-β, and chemokines, as well as increased collagen deposition and airway hyperreactivity to methacholine were all clearly sensitive to IL-13–PE. In addition, IL-13–PE inhibited both IL-13–induced proliferation of cultured lung fibroblasts from silicotic mice and silica-induced IL-8 generation from A549 cells. In conclusion, our findings show that therapeutic treatment with IL-13–PE can reverse important pathological features caused by inhalation of silica particles, suggesting that this recombinant immunotoxin is a promising molecular template in drug discovery for the treatment of silicosis.

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Histopathological Changes in Enlarged Thoracic Lymph Nodes during the Development of Silicosis in Rats

Cited by 35 publications

References 7 publications

Silica binding and toxicity in alveolar macrophages

Silica binding and toxicity in alveolar macrophages

Pathological Study of Chronic Pulmonary Toxicity Induced by Intratracheally Instilled Asian Sand Dust (Kosa)

IL-13 Immunotoxin Accelerates Resolution of Lung Pathological Changes Triggered by Silica Particles in Mice

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