Immunotoxic Effects of the Color Additive Caramel Color III: Immune Function Studies in Rats

Houben, Geert; Penninks, André; Seinen, Willem; Vos, J.G.; Loveren, Henk Van

doi:10.1006/faat.1993.1004

Cited by 17 publications

(4 citation statements)

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“…In the rat, this compound rapidly reduced the number of B and T lymphocytes in peripheral blood and reduced lymphocyte numbers in spleen and lymph nodes. THIinduced immunosuppression is thought to be due to inhibited migration of mature thymocytes into the periphery (15). Most of the thymotoxic and immunosuppressive compounds also affect secondary lymphoid organs and tissues, as illustrated in Figure 8a-c by the effect of cyclophosphamide on the spleen.…”

Section: Examples Of Induced Immunotoxic Changesmentioning

confidence: 99%

Histopathologic Approaches to Detect Changes Indicative of Immunotoxicity

Kuper¹,

et al. 2000

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Toxicologic pathology is crucial in the identification and characterization of health effects following exposure to xenobiotics, mainly in toxicity experiments in rodents. Regarding regulatory toxicology, histopathology of lymphoid organs and tissues is a cornerstone in the identification of immunotoxic compounds. A 2-tier testing system is usually employed in which the first tier is a general screen for (immuno)toxicity and the second tier consists of specific immune function studies, including host resistance tests or mechanistic studies. The role attributed to histopathology of lymphoid organs in the updated Organisation for Economic Cooperation and Development and Food and Drug Administration guidelines requires improvement and standardization of the histopathology procedures. Optimalization and standardization was started in an international collaborative immunotoxicity study (ICICIS). However, several problems were left unaddressed, mostly because of the few compounds tested in this study. Based on the results of the ICICIS study and the morphologic changes induced by immunotoxic/immunomodulatory compounds observed in other investigations, suggestions are given to further improve the identification and (semi)quantification of histopathologic changes in lymphoid organs and tissues.

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Section: Examples Of Induced Immunotoxic Changesmentioning

confidence: 99%

Histopathologic Approaches to Detect Changes Indicative of Immunotoxicity

Kuper¹,

et al. 2000

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“…By reducing local tissue S1P levels, SPL generated a chemotactic gradient that was essential for guiding S1P1-expressing mature thymocytes away from thymus and into the blood 23 . The importance of the chemotactic S1P gradient was confirmed by the demonstration that inhibition of SPL activity by tetrahydroxybutylimidazole — a compound found in caramel food coloring known previously to cause lymphopenia 24 — also blocked thymic egress when administered to mice, consistent with the lymphopenia characteristic of global SPL knockout mice 23, 25 . Thus, an S1P chemotactic gradient combined with a receptor system for sensing that gradient are the two fundamental requirements that enable mature naïve T cells to enter the circulation.…”

Section: The Contribution Of S1p Catabolism and Transport To Thymic Ementioning

confidence: 71%

The low down on sphingosine-1-phosphate lyase as a regulator of thymic egress

Saba¹

2017

J Immunological Sci

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After undergoing positive and negative selection in the thymus, surviving mature T cells egress from the thymic parenchyma and enter the bloodstream to participate in adaptive immunity. Thymic egress requires signals mediated by sphingosine-1-phosphate (S1P), a bioactive lipid that serves as the ligand for a family of G protein-coupled receptors (S1P1-5) expressed on many cell types, including T cells. In the final stage of their development, T cells upregulate S1P1 expression on the cell surface, which enables them to recognize and respond to a chemotactic S1P gradient that lures them into the bloodstream. The gradient is generated by an S1P source close to the site of egress combined with an S1P sink generated by the actions of S1P catabolic enzymes including S1P lyase (SPL), the only enzyme that irreversibly degrades S1P. The requisite contribution of SPL to thymic egress is demonstrated by the profound lymphopenia observed in SPL knockout (KO) mice and wild type mice treated with SPL inhibitors. SPL is robustly expressed in thymic epithelial cells (TECs), which make up the stromal reticular network of the thymus. However, TEC SPL was recently found to be dispensable for thymic egress. In contrast, deletion of SPL in dendritic cells (DCs) — which represent only a small percent of thymic stroma — disrupts the S1P gradient and blocks thymic egress. These recent observations identify DCs as homeostatic regulators of thymic export through the actions of SPL, thereby adding one more piece to the complex puzzle of how S1P signaling contributes to the regulation of T cell trafficking.

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“…Dexamethasone and some organotin compounds such as dicotyltin dichloride and 2-acetyl-4(5)-tetrahydroxybutylimidazole have been associated with decreased corticomedullary ratios. 57 If both decreased and increased corticomedullary ratios are present, then the term “altered corticomedullary ratio” may be used. 20,58,59…”

Section: Enh Corticomedullary Ratio Decreasedmentioning

confidence: 99%

Nonproliferative and Proliferative Lesions of the Rat and Mouse Hematolymphoid System

Willard-Mack

Elmore

Hall³

et al. 2019

Toxicol Pathol

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The INHAND Project (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) is a joint initiative of the Societies of Toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP), and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative changes in rats and mice. The purpose of this publication is to provide a standardized nomenclature for classifying changes observed in the hematolymphoid organs, including the bone marrow, thymus, spleen, lymph nodes, mucosa-associated lymphoid tissues, and other lymphoid tissues (serosa-associated lymphoid clusters and tertiary lymphoid structures) with color photomicrographs illustrating examples of the lesions. Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous lesions as well as lesions induced by exposure to test materials. The nomenclature for these organs is divided into 3 terminologies: descriptive, conventional, and enhanced. Three terms are listed for each diagnosis. The rationale for this approach and guidance for its application to toxicologic pathology are described in detail below.

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Immunotoxic Effects of the Color Additive Caramel Color III: Immune Function Studies in Rats

Cited by 17 publications

References 0 publications

Histopathologic Approaches to Detect Changes Indicative of Immunotoxicity

Histopathologic Approaches to Detect Changes Indicative of Immunotoxicity

The low down on sphingosine-1-phosphate lyase as a regulator of thymic egress

Nonproliferative and Proliferative Lesions of the Rat and Mouse Hematolymphoid System

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