Alterations in fetal thymic and liver hematopoietic cells as indicators of exposure to developmental immunotoxicants.

Holladay, Steven D.; Luster, Michael I.

doi:10.1289/ehp.96104s4809

Cited by 27 publications

(16 citation statements)

References 27 publications

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“…Thymic atrophy, a key event that may lead to inefficient functioning of the immune system, has been reported in bacterial and viral infections, graft versus host-disease, tumor development, and following exposure to immunosuppressive chemicals (Frawley et al, 2011;Haynes et al, 2000;Holladay & Luster, 1996;Taub & Longo, 2005). In the present study, ANE (25 mg/kg) administration reduced the number of both immature thymic cells and mature CD4 þ and CD8 þ lymphocytes.…”

Section: Discussionsupporting

confidence: 54%

“…For example, mice exposed to halogenated and polycyclic aromatic hydrocarbons demonstrate impaired thymocyte maturation and increased susceptibility to infections (Drela, 2006;Lutz et al, 1998). There are diverse mechanisms involved in chemicalinduced thymus atrophy, such as alterations in bone marrowderived thymocyte precursors, direct toxic effects on thymocytes or thymic epithelial cells, and/or induction of adrenal glucocorticoids (Comment et al, 1992;Holladay & Luster, 1996;Lundberg, 1991). It has been demonstrated that glucocorticoids inhibit thymocyte functions and induce thymocyte apoptosis in vivo (Young et al, 1981).…”

Section: Discussionmentioning

confidence: 99%

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Impairment of thymocyte function via induction of apoptosis by areca nut extract

Lee

Lin

Liu

et al. 2013

Journal of Immunotoxicology

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Areca quid (AQ) chewing is a popular oral habit, especially in Southeast Asia cultures, in which children may be engaged in the addictive habit early in their lives. Extracts of areca nuts, the main component of AQ, have been shown to affect the functionality of T-cells. However, the potential influence of ANE on the development of T-cells is unknown. This study, therefore, investigated the impact of areca nut extracts (ANE) on thymocytes and the potential mechanisms of action. Mice administered intraperitoneally with ANE at 1, 5, or 25 mg/kg daily for 5 days showed significant dose-dependent reductions in thymocyte viability. A marked decrease in the total number of thymocytes and the proportion of thymic CD4 þ CD8þ cells was observed in the 25 mg ANE/kg-treated mice, whereas the proportion of CD4 and CD8 single positive and CD4À CD8 À cells was significantly increased. Further examination on the functionality of thymocytes showed that ANE suppress IL-2 production both ex vivo and in vitro. These results suggest that ANE may attenuate the development and functionality of thymic T-cells. ANE also directly induced apoptosis in thymic T-cells through activation of casapase-3 and apoptosis inducing factor (AIF). Collectively, the data suggested that the thymus is a sensitive target to ANE. Early exposure to ANE may interfere with the development and functionality of thymic T-cells.

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Impairment of thymocyte function via induction of apoptosis by areca nut extract

Lee

Lin

Liu

et al. 2013

Journal of Immunotoxicology

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“…+ fetal thymocytes and significantly increase the relative percentage of CD4-CD8-and CD4-CD8 + fetal thymocyte subsets (Holladay and Luster, 1996).…”

Section: Immune Effects Of Tcdd In Rodentsmentioning

confidence: 93%

Perinatal TCDD exposure and the adult onset of autoimmune disease

Gogal

Holladay

2008

Journal of Immunotoxicology

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“…The carcinogenic potential of pyrethroids was also reported on the murine model (9). A few recent studies revealed that besides blocking neurotransmission, both pyrethroids and organophosphate pesticides can cause immunosuppression and deregulation of many signalling molecules (10)(11)(12)(13)(14)(15). Organophosphates (derivatives of phosphonic acid) and systemic azole fungicides have profound cytotoxic activities, too (16,17).…”

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confidence: 99%

Altered canonical hedgehog-gli signalling axis in pesticide-induced bone marrow aplasia mouse model

Chaklader¹,

Das²,

Pereira³

et al. 2012

Archives of Industrial Hygiene and Toxicology

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The mechanistic interplay between pesticide exposure and development of marrow aplasia is not yet well established but there are indices that chronic pesticide exposure in some instances causes marrow aplasia like haematopoietic degenerative condition in human beings. Canonical Hedgehog (Hh) signalling has multiple roles in a wide range of developmental processes, including haematopoiesis. The present study was designed to explore the status of four important components of the canonical Hedgehog signalling cascade, the Sonic Hedgehog (Shh), Ptch1, Smo, and Gli1, in a mouse model of chronic pesticide-induced bone marrow aplasia. We used 5 % aqueous mixture of pesticides (chlorpyriphos, prophenophos, cypermethrin, alpha-methrin, and hexaconazole) for inhalation and dermal exposure of 6 hours per day and 5 days a week up to 90 days. Murine bone marrow aplasia related to chronic pesticide treatment was confi rmed primarily by haemogram, bone marrow cellularity, short term bone marrow explant culture for cellular kinetics, bone marrow smear, and fl ow cytometric Lin -Sca-1 + C-kit + extracellular receptor expression pattern. Later, components of hedgehog signalling were analysed in the bone marrow of both control and pesticide-treated aplastic groups of animals. The results depicted pancytopenic feature of peripheral blood, developmental anomaly of neutrophils, depression of primitive stem and progenitor population along with Shh, Ptch1, Smo and Gli1 expression in aplasia group. This investigation suggests that pesticide-induced downregulation of two critically important proteins -Ptch1 and Gli1 -inside the haematopoietic stem and progenitor cell population impairs haematopoietic homeostasis and regeneration mechanism in vivo concurrent with bone marrow aplasia. Arh Hig Rada Toksikol 2012;63:271-282 A surge of numerous organophosphates, pyrethroids (analogs of naturally occurring phytopyrethrins), and thiazole fungicides replaced DDT after the ban in 1993. Depending on the physiological activity, synthetic pyrethroids are of two distinct types: Type I pyrethroids, which do not contain the α-cyano group, and Type II pyrethroids, which have the α-cyano group (1-3). Previous studies have affi rmed the genotoxic and/or cytotoxic effects of Type II pyrethroids such as cyfl uthrin, cypermethrin etc. (4-9). The carcinogenic potential of pyrethroids was also reported on the murine model (9). A few recent studies revealed that besides blocking neurotransmission, both pyrethroids and organophosphate pesticides can cause Unauthenticated Download Date | 5/12/18 12:23 AM KEY WORDS: bone marrow suppression, haematopoietic stem cell, patched, smoothened, sonic hedgehog Chaklader M, et al. ALTERED HH-GLI SIGNALLING IN PESTICIDE-INDUCED BONE MARROW APLASIA

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Alterations in fetal thymic and liver hematopoietic cells as indicators of exposure to developmental immunotoxicants.

Cited by 27 publications

References 27 publications

Impairment of thymocyte function via induction of apoptosis by areca nut extract

Impairment of thymocyte function via induction of apoptosis by areca nut extract

Perinatal TCDD exposure and the adult onset of autoimmune disease

Altered canonical hedgehog-gli signalling axis in pesticide-induced bone marrow aplasia mouse model

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