Contributions of Nonhematopoietic Cells and Mediators to Immune Responses: Implications For Immunotoxicology

Kaplan, Barbara L. F.; Li, Jinze; LaPres, John J.; Pruett, Stephen B.; Karmaus, Peer W. F.

doi:10.1093/toxsci/kfv060

Cited by 10 publications

(2 citation statements)

References 220 publications

(245 reference statements)

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“…It is important to note this study separated thymocytes from TSC. The results thus cannot exclude a likelihood that TSC have a role in EDC-mediated toxicities in vivo (Kaplan et al 2015). Rather, it shows that in addition to potential TSC effects, EDC (like DES and HPTE) have direct effects on embryonic thymocytes similar to sustained thymocyte-thymocyte interactions that support negative selection (Melichar et al 2015).…”

Section: Discussionmentioning

confidence: 99%

Methoxychlor metabolite HPTE alters viability and differentiation of embryonic thymocytes from C57BL/6 mice

Leung-Gurung

Cobb

Mourad

et al. 2018

Journal of Immunotoxicology

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Endocrine-disrupting chemicals (EDC) are widespread in the built and natural environments. Heightened public awareness of their potential danger has led to concern about whether EDC and their metabolites have significant negative biological effects. Studies have shown that EDC like DDT and other organochlorine pesticides, such as methoxychlor (MXC), have adverse effects on immune cells, but no studies have addressed the impact of HPTE, the primary metabolite of MXC. To elucidate the presence and significance of HPTE adverse effects, this study explored the impact of HPTE on a critical window and component of immune system development, embryonic T-cell development. Lesions at this phase of development can lead to lifelong immune dysfunction and increased incidence of immune disease, such as autoimmunity. Embry-onic thymocytes (GD 16–18) from C57BL/6 mice were subjected to an in vitro differentiation culture that mimicked early steps in thymocyte development in the presence of 0.005, 0.05, 0.5, 5, or 50 μM HPTE, or a model endocrine disruptor, DES. The results indicated that compared to the vehicle control, HPTE and DES induced death of thymocytes. Annexin-V staining and Caspase 8, markers of programmed cell death, revealed that the loss of cells was due at least in part to induction of apoptosis. Moreover, HPTE-induced cell death not only resulted in selective loss of double positive thymocytes, but also loss of developing CD4 intermediate cells (post-double positive partially-differentiated thymocyte population). Phenotypic analysis of thymocyte maturation (T-cell receptor, TCR) and TCR ligation (CD5) surface markers revealed that surviving embryonic thymocytes expressed low levels of both. Taken together these data demonstrate that immature embryonic thymocytes are sensitive to HPTE exposure and that HPTE exposure targets thymocyte populations undergoing critical differentiation steps. These findings suggest HPTE may play a pivotal role in MXC exposure-induced immune dysfunction.

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Section: Discussionmentioning

confidence: 99%

Methoxychlor metabolite HPTE alters viability and differentiation of embryonic thymocytes from C57BL/6 mice

Leung-Gurung

Cobb

Mourad

et al. 2018

Journal of Immunotoxicology

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“…Immune cells are essential for protection from pathogenic infections and preventing or reducing neoplastic growth [23]. The sophisticated molecular mechanisms can prove how the immune system could combat cancer cells by recognizing cancer cells and killing them [24].…”

Section: Discussionmentioning

confidence: 99%

Optimizing the Method of Cell Separation from Bile of Patients with Cholangiocarcinoma for Flow Cytometry

Xia

Gao

Wang

et al. 2019

Gastroenterology Research and Practice

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Analysis of the change of the cells in bile is an evolving research field in biliary pathophysiology and has potential value in diagnosis and therapy. However, laboratory studies of cell in bile across the world are scarce. Bile was collected from the clinical patients with cholangiocarcinoma (CC). To optimize the cell separation method in bile of patients with CC, we studied the factors that may affect cell vitality in bile including the dilution buffer, centrifugal force, centrifugal time, and store time and temperature. Then these factors were modified and performance was evaluated by flow cytometry with respect to the percentage and total yield of viable cells. The separated cells from bile were stained with CD3, CD4, CD8, CD56, TCRγ/δ, CD16, CD14, HLA-DR, CD33, CD15, CD11b, lineage cocktail (CD3, CD14, CD19, CD20, and CD56), CD66b, and CD45 antibodies. The different buffer solutions were joined in bile of patients with CC; experiment results show that the different dilutions have nearly no effect on the ratio of cells in bile by flow cytometry. The best centrifugal procedure was 300 g, 10 min. Bile should be stored at 4°C rather than at normal temperature. Our study further showed that the shorter time of the bile storage, the higher viability of the cell, and immune cells existed in cells isolated from bile. Evaluating bile cell viability is necessary to evaluate method performance.

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Flow Cytometry for the Immunotoxicologist

Espenschied

Tighe

Gowdy

2018

Methods in Molecular Biology

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Assessing the immunotoxicity of xenobiotics by current regulatory testing has revealed compounds that can cause immunosuppression and stimulation. Flow cytometry is a cutting edge technique that can provide data on how toxicants can alter the quality and quantity of the immune response after exposure. Here we describe protocols for how to use flow cytometry to measure the immune response in multiple rodent organs (blood and lymphoid and nonlymphoid) as well as in novel models recently being utilized in the field of toxicology. These methods can be used for current testing and to determine mechanisms by which a xenobiotic can cause immunotoxicity.

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Contributions of Nonhematopoietic Cells and Mediators to Immune Responses: Implications For Immunotoxicology

Cited by 10 publications

References 220 publications

Methoxychlor metabolite HPTE alters viability and differentiation of embryonic thymocytes from C57BL/6 mice

Methoxychlor metabolite HPTE alters viability and differentiation of embryonic thymocytes from C57BL/6 mice

Optimizing the Method of Cell Separation from Bile of Patients with Cholangiocarcinoma for Flow Cytometry

Flow Cytometry for the Immunotoxicologist

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