Evidence for arsenic as the immunosuppressive component of gallium arsenide

Burns, L A; Sikorski, Elizabeth E.; Saady, Joseph J.; Munson, Albert E.

doi:10.1016/0041-008x(91)90298-s

Cited by 78 publications

(30 citation statements)

References 25 publications

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“…GaAs may cause a local inflammatory reaction in the peritoneum, leading to the augmented functional capability of the macrophages, similar to the pulmonary inflammation induced after intratracheal instillation of the chemical [32,33]. On the other hand, GaAs dissociates in vivo, and gallium and arsenic components are present in the blood and various organs up to 14 days after a single exposure by intratracheal, oral, or intraperitoneal administration [34][35][36]. Gallium is a competitive inhibitor of zinc-and iron-dependent enzymes [33,37].…”

Section: Discussionmentioning

confidence: 99%

Gallium arsenide differentially affects processing of phagolysosomal targeted antigen by macrophages

Lewis

Hartmann

McCoy

1998

Journal of Leukocyte Biology

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Gallium arsenide, a semiconductor utilized in the electronics industry, causes immunosuppression in animals. The chemical's effect on macrophages to process antigen for activating pigeon cytochrome-specific helper T cell hybridoma was investigated. Mice were administered 200 mg/kg gallium arsenide or vehicle intraperitoneally. Fiveday exposure suppressed processing by splenic macrophages but augmented processing by thioglycollate-elicited and resident peritoneal macrophages. Cytochrome coupled to latex beads was targeted to phagolysosomes to examine processing in lysosomes. Cytochrome beads required phagocytosis for processing and were located in phagolysosomes. Gallium arsenide did not alter the phagocytic ability of macrophages. Peritoneal macrophages normally processed the targeted antigen, indicating that gallium arsenide influenced compartment(s) preceding lysosomes. However, the processing efficiency of exposed splenic macrophages depended on the size of particulate cytochrome, suggesting that processing varied in phagolysosomes of different sizes. Gallium arsenide impacted different intracellular compartments in these macrophages, perhaps contributing to systemic immunotoxicity and local inflammation caused by exposure.

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Section: Discussionmentioning

confidence: 99%

Gallium arsenide differentially affects processing of phagolysosomal targeted antigen by macrophages

Lewis

Hartmann

McCoy

1998

Journal of Leukocyte Biology

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“…In addition, the immunization of GaAs-treated mice with sheep red blood cells produced a 50% decrease in CD4 + splenic cells after 24 h (Burns and Munson, 1993). The arsenic component of GaAs was shown to be the major contributor to the observed induced immunosuppression (Burns et al, 1991). Sengupta and Bishayi (2002) revealed that arsenic significantly decreased murine splenocyte phagocytic activity.…”

Section: Introductionmentioning

confidence: 99%

Protective effect of curcumin against arsenic-induced apoptosis in murine splenocytesin vitro

Khan

Vala

Nabi

et al. 2011

Journal of Immunotoxicology

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“…An alarming number of toxicity cases have been reported in these areas (1), in which arsenic has been found to cause immunotoxicity, immunosuppression, skin lesions, and increased risk of cancer (2)(3)(4)(5)(6). At the same time, renewed attention has been created due to the therapeutic application of arsenic in the treatment of lymphoid and hemopoietic neoplasmas such as acute promyelocytic leukemia (7).…”

mentioning

confidence: 99%

“…Caspase activation may (13,14) or may not (15) be associated with arsenic-induced apoptosis of neoplastic cells. Arsenite has also been shown to induce activation of mitogen-activated protein kinase (MAPK) 3 (2) family member proteins, some of which may play a key role in apoptosis induction in leukemia cells (10). These observations in studies using neoplastic cells, which have partially elucidated the mechanism of arsenite-induced apoptosis, have not, however, enabled clarification of the total signal cascade from the cell surface to the nucleus for arsenite-induced apoptosis of normal lymphocytes, which may be important for a better understanding of the arsenite-induced immunotoxicity and immunosuppression.…”

mentioning

confidence: 99%

Arsenite Induces Apoptosis of Murine T Lymphocytes Through Membrane Raft-Linked Signaling for Activation of c-Jun Amino-Terminal Kinase

Hossain

Akhand

Kato

et al. 2000

The Journal of Immunology

112

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Because of its dual roles in acute toxicity and in therapeutic application in cancer treatment, arsenic has recently attracted a renewed attention. In this study, we report NaAsO2-induced signal cascades from the cell surface to the nucleus of murine thymic T lymphocytes that involve membrane rafts as an initial signal transducer. NaAsO2 induced apoptosis through fragmentation of DNA, activation of caspase, and reciprocal regulation of Bcl-2/Bax with the concomitant reduction of membrane potential. We demonstrated that NaAsO2-induced caspase activation is dependent on curcumin-sensitive c-Jun amino-terminal kinase and barely dependent on SB203580-sensitive p38 kinase or PD98059-sensitive extracellular signal-regulated kinase. Additionally, staurosporine, which severely inhibited the activation of mitogen-activated protein (MAP) family kinases and c-Jun, partially blocked the NaAsO2-mediated signal for poly(ADP-ribose) polymerase (PARP) degradation. Potentially as the initial cell surface event for intracellular signaling, NaAsO2 induced aggregation of GPI-anchored protein Thy-1 and superoxide production. This Thy-1 aggregation and subsequent activation of MAP family kinase and c-Jun and the degradation of PARP induced by NaAsO2 were all inhibited by DTT, suggesting the requirement of interaction between arsenic and protein sulfhydryl groups for those effects. β cyclodextrin, which sequestrates cholesterol from the membrane rafts, inhibited NaAsO2-induced activation of protein tyrosine kinases and MAP family kinases, degradation of PARP, and production of superoxide. In addition, β cyclodextrin dispersed NaAsO2-induced Thy-1 clustering. These results suggest that a membrane raft integrity-dependent cell surface event is a prerequisite for NaAsO2-induced protein tyrosine kinase/c-Jun amino-terminal kinase activation, superoxide production, and downstream caspase activation.

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Evidence for arsenic as the immunosuppressive component of gallium arsenide

Cited by 78 publications

References 25 publications

Gallium arsenide differentially affects processing of phagolysosomal targeted antigen by macrophages

Gallium arsenide differentially affects processing of phagolysosomal targeted antigen by macrophages

Protective effect of curcumin against arsenic-induced apoptosis in murine splenocytesin vitro

Arsenite Induces Apoptosis of Murine T Lymphocytes Through Membrane Raft-Linked Signaling for Activation of c-Jun Amino-Terminal Kinase

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