Kupffer cells participate in 2-butoxyethanol-induced liver hemangiosarcomas

Kamendulis, Lisa M.; Corthals, Stacy M.; Klaunig, James E.

doi:10.1016/j.tox.2010.02.006

Cited by 11 publications

(4 citation statements)

References 29 publications

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“…Moreover, hepatic levels of IL-13, the major inducing factor for fibrosis in schistosomiasis, were also unchanged as a result of IL-10R blockade (Figure 3D). However, we found evidence of hepatic bleeding, apparent as red blood cells and plasma in extravascular spaces with a loss of cellular structure (Figure 3E), and marked deposition of hemosiderin (an indicator of bleeding [24], [25]) (Figure 3F), in mice that were treated with anti-IL-10R. Hemosiderin was localized to F4/80 + cells that exhibit macrophage-like morphology (Figure 3F).…”

Section: Resultsmentioning

confidence: 95%

IL-10R Blockade during Chronic Schistosomiasis Mansoni Results in the Loss of B Cells from the Liver and the Development of Severe Pulmonary Disease

et al. 2012

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In schistosomiasis patients, parasite eggs trapped in hepatic sinusoids become foci for CD4+ T cell-orchestrated granulomatous cellular infiltrates. Since the immune response is unable to clear the infection, the liver is subjected to ongoing cycles of focal inflammation and healing that lead to vascular obstruction and tissue fibrosis. This is mitigated by regulatory mechanisms that develop over time and which minimize the inflammatory response to newly deposited eggs. Exploring changes in the hepatic inflammatory infiltrate over time in infected mice, we found an accumulation of schistosome egg antigen-specific IgG1-secreting plasma cells during chronic infection. This population was significantly diminished by blockade of the receptor for IL-10, a cytokine implicated in plasma cell development. Strikingly, IL-10R blockade precipitated the development of portal hypertension and the accumulation of parasite eggs in the lungs and heart. This did not reflect more aggressive Th2 cell responsiveness, increased hepatic fibrosis, or the emergence of Th1 or Th17 responses. Rather, a role for antibody in the prevention of severe disease was suggested by the finding that pulmonary involvement was also apparent in mice unable to secrete class switched antibody. A major effect of anti-IL-10R treatment was the loss of a myeloid population that stained positively for surface IgG1, and which exhibited characteristics of regulatory/anti-inflammatory macrophages. This finding suggests that antibody may promote protective effects within the liver through local interactions with macrophages. In summary, our data describe a role for IL-10-dependent B cell responses in the regulation of tissue damage during a chronic helminth infection.

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Section: Resultsmentioning

confidence: 95%

IL-10R Blockade during Chronic Schistosomiasis Mansoni Results in the Loss of B Cells from the Liver and the Development of Severe Pulmonary Disease

et al. 2012

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“…Recently, studies have presented the hypothesis that Kupffer cells modulate 2-butoxyethanol-induced endothelial cell DNA synthesis, which may contribute to hemangiosarcoma. 25,26 The presence of TBEP in some commercial heparin samples and not in the raw material suggests that it may be a problem related to industrial processes, in contrast to that with the OSCS observed in some Brazilian heparins which was possibly present in the raw material originating from China, as did those contaminated batches from Baxter during the heparin crisis.…”

Section: Discussionmentioning

confidence: 99%

A robust method to quantify low molecular weight contaminants in heparin: detection of tris(2-n-butoxyethyl) phosphate

Sassaki

Riter

Santana-Filho

et al. 2011

Analyst

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Recently, oversulfated chondroitin sulfate (OSCS) was identified in contaminated heparin preparations, which were linked to several adverse clinical events and deaths. Orthogonal analytical techniques, namely nuclear magnetic resonance (NMR) and capillary electrophoresis (CE), have since been applied by several authors for the evaluation of heparin purity and safety. NMR identification and quantification of residual solvents and non-volatile low molecular contaminants with USP acceptance levels of toxicity was achieved 40-fold faster than the traditional GC-headspace technique, which takes ~120 min against ~3 min to obtain a (1)H NMR spectrum with a signal/noise ratio of at least 1000/1. The procedure allowed detection of Class 1 residual solvents at 2 ppm and quantification was possible above 10 ppm. 2D NMR techniques (edited-HSQC (1)H/(13)C) permitted visualization of otherwise masked EDTA signals at 3.68/59.7 ppm and 3.34/53.5 ppm, which may be overlapping mononuclear heparin signals, or those of ethanol and methanol. Detailed NMR and ESI-MS/MS studies revealed a hitherto unknown contaminant, tris(2-n-butoxyethyl) phosphate (TBEP), which has potential health risks.

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“…A current model of 2-BE effects seen in mice suggests that 2-BE induces macrophage activation and inflammation in the liver involving Kupffer cells (liver macrophages). Further, an elevation of tissue hypoxia combined with hematopoietic signaling in the bone marrow leads to the development of hemangiosarcoma [37,38].…”

Section: Glycol Ethersmentioning

confidence: 99%

Effects of Endocrine Disrupters on Immune Function and Inflammation

Dietert¹

2015

Endocrine Disruption and Human Health

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Kupffer cells participate in 2-butoxyethanol-induced liver hemangiosarcomas

Cited by 11 publications

References 29 publications

IL-10R Blockade during Chronic Schistosomiasis Mansoni Results in the Loss of B Cells from the Liver and the Development of Severe Pulmonary Disease

IL-10R Blockade during Chronic Schistosomiasis Mansoni Results in the Loss of B Cells from the Liver and the Development of Severe Pulmonary Disease

A robust method to quantify low molecular weight contaminants in heparin: detection of tris(2-n-butoxyethyl) phosphate

Effects of Endocrine Disrupters on Immune Function and Inflammation

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