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Were the wrong cells studied?
Toxicology Letters 232 (2015) 542–543
Contents lists available at ScienceDirect
Toxicology Letters journal homepage: www.elsevier.com/locate/toxlet
Letter to the Editor Were the wrong cells studied?
A R T I C L E I N F O
A B S T R A C T
Article history: Received 14 August 2014 Accepted 2 October 2014 Available online 13 October 2014
Peripheral blood lymphocytes (PBL) studying the effects of dioxins and dioxin-like compounds in vitro is not correct. Peripheral lymphocytes in general (Th1, Th2) do not have an Ah-receptor. Polymorphonuclear leucocytes (PMN’s) are more logical to use. ã 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Lymphocytes Polymorphonuclear leucocytes Ah-receptor Dioxin Dioxin-like compound Toxic equivalent factor (TEF)
Dear editor, Your journal recently published a paper by Karin van Ede E.A. with the title: Differential Relative Effect Potencies of some Dioxinlike Compounds in Human Peripheral Blood Lymphocytes and Murine Splenic Cells (van Ede et al., 2014). In the methods of the article the authors describe that they used peripheral blood lymphocytes (PBL). No references are given. Generally, lymphocytes do not have an Ah-receptor, with the exception of only a small subset of Th17 cells (Stockinger et al., 2008; Veldhoen et al., 2008). This weakens the methodology used, as an Ah-receptor is a “conditio sine qua non” for testing effects of dioxins and dioxin-like compounds. The results and conclusions of the paper related to the use of the human cells must therefore be challenged. Early in the haematopoiesis differentiation takes place into a common myeloid progenitor and a lymphoid progenitor. The myeloid branch develops the Ah-receptor (Ackerman et al., 1989). In blood of adults the majority of the leukocytes are polymorphonuclear leukocytes (PMN) and lymphocytes (PBL), the former developing from the myeloid branch and the latter from the lymphoid branch. In human studies, specifically studies of the PMNs and thrombocytes, the myeloid branch seems to consistently be influenced in a negative manner by dioxin-like compounds (Pluim et al., 1994; Weisglas-Kuperus et al., 1995; ten Tusscher et al., 2003; Leijs et al., 2009). Based on the findings in humans and in mice (Ackerman et al., 1989) we would postulate that using human lymphocytes for studying the effects of dioxins and dioxin-like compounds in vitro is not correct. Studying the effects on PMNs would be more logical. It must, however, be borne in mind that these cells are produced in
http://dx.doi.org/10.1016/j.toxlet.2014.10.002 0378-4274/ ã 2014 Elsevier Ireland Ltd. All rights reserved.
bone marrow that has been exposed to dioxins for years. Epigenetic changes therefore also need to be considered, as shown in the upregulation of haemoglobin genes in the Seveso population (McHale et al., 2007). The influence of hypoxia must also be taken taken into account (Vorrink et al., 2014). Conflict of interest The authors declare that there are no conflicts of interest. Transparency document The Transparency document associated with this article can be found in the online version. References Ackerman, M.F., Gasiewicz, T.A., Lamm, K.R., Germolec, D.R., Luster, M.I., 1989. Selective inhibition of polymorphonuclear neutrophil activity by 2,3,7,8tetrachlorodibenzo-p-dioxin. Toxicol. Appl. Pharmacol. 101 (3), 470–480. Leijs, M.M., Koppe, J.G., Olie, K., van Aalderen, W.M.C., de Voogt, P., ten Tusscher, G. W., 2009. Effects of dioxins, PCBs and PBDEs on immunology and haematology in adolescents. J. Environ. Sci. Technol. 43, 7646–7951. McHale, C.M., Zhang, L., Hubbard, A.E., Zhao, X., Baccarelli, A., Pesatori, A.C., et al., 2007. Microarray analysis of gene expression in peripheral blood mononuclear cells from dioxin-exposed human subjects. Toxicology 229, 101–113. Pluim, H.J., Koppe, J.G., Olie, K., van der Slikke, J.W., Slot, P.C., van BoxTel, C.J., 1994. Clinical laboratory manifestations of exposure to background levels of dioxins in the perinatal period. Acta Paediatr. 83 (6), 583–587 Jun. Stockinger, B., Veldhoen, M., Hirota, K., 2008. AhR expression and its functional consequences on the Th17 effector T cell subset. Organohal. Compd. 70. ten Tusscher, G.W., Steerenberg, P.A., van Loveren, H., Vos, J.G., von dem Borne, A.E.G. K., Westra, M., et al., 2003. Persistent hematologic and immunologic disturbances in 8-year-Old Dutch children associated with perinatal dioxin exposure. Environ. Health Perspect. 111, 1519–1523. van Ede, K., Gaisch, K.P.J., Van den Berg, M., van Duursen, M.B.M., 2014. Differential relative effect ootencies of some dioxin-like compounds in human peripheral blood lymphocytes and murine splenic cells. Toxicol. Lett. 226, 43–52.
Letter to the Editor / Toxicology Letters 232 (2015) 542–543 Veldhoen, M., Hirota, K., Westendorff, A.M., Buer, J., Dumoutier, L., Renuald, J.C., et al., 2008. The aryl hydrocarbon receptor links Th17-cell-mediated autoimmunity to environmental toxins. Nature 453, 106–109 101038/ nature06881. Vorrink, S.U., Severson, P.L., Kulak, M.V., Futscher, B.W., Domann, F.E., 2014. Hypoxia perturbs aryl hydrocarbon receptor signaling and CYP1A1 expression induced by PCB 126 in human skin and liver-derived cell lines. Toxicol. Appl. Pharmacol. 274, 408–416. Weisglas-Kuperus, N., Sas, T.C.J., Koopman-Esseboom, C., van der Zwan, C.W., de Ridder, M.A.J., Beishuizen, A., et al., 1995. Ímmunologic effects of background prenatal and postnatal exposure to dioxins and polychlorinated biphenyls in Dutch Infants. Pediatr. Res. 38, 404–410.
543
Janna Koppea,* Gavin W. Ten Tusscherb a University of Amsterdam, Emma Children’s Hospital-AMC, Dept. of Pulmonology, Hollandstraat 6, 3634 AT Loenersloot, The Netherlands b
Department of Paediatrics and Neonatology, Westfriesgasthuis, Hoorn, The Netherlands * Corresponding author. Tel.: +31 294291589.
Contents lists available at ScienceDirect
Toxicology Letters journal homepage: www.elsevier.com/locate/toxlet
Letter to the Editor Were the wrong cells studied?
A R T I C L E I N F O
A B S T R A C T
Article history: Received 14 August 2014 Accepted 2 October 2014 Available online 13 October 2014
Peripheral blood lymphocytes (PBL) studying the effects of dioxins and dioxin-like compounds in vitro is not correct. Peripheral lymphocytes in general (Th1, Th2) do not have an Ah-receptor. Polymorphonuclear leucocytes (PMN’s) are more logical to use. ã 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Lymphocytes Polymorphonuclear leucocytes Ah-receptor Dioxin Dioxin-like compound Toxic equivalent factor (TEF)
Dear editor, Your journal recently published a paper by Karin van Ede E.A. with the title: Differential Relative Effect Potencies of some Dioxinlike Compounds in Human Peripheral Blood Lymphocytes and Murine Splenic Cells (van Ede et al., 2014). In the methods of the article the authors describe that they used peripheral blood lymphocytes (PBL). No references are given. Generally, lymphocytes do not have an Ah-receptor, with the exception of only a small subset of Th17 cells (Stockinger et al., 2008; Veldhoen et al., 2008). This weakens the methodology used, as an Ah-receptor is a “conditio sine qua non” for testing effects of dioxins and dioxin-like compounds. The results and conclusions of the paper related to the use of the human cells must therefore be challenged. Early in the haematopoiesis differentiation takes place into a common myeloid progenitor and a lymphoid progenitor. The myeloid branch develops the Ah-receptor (Ackerman et al., 1989). In blood of adults the majority of the leukocytes are polymorphonuclear leukocytes (PMN) and lymphocytes (PBL), the former developing from the myeloid branch and the latter from the lymphoid branch. In human studies, specifically studies of the PMNs and thrombocytes, the myeloid branch seems to consistently be influenced in a negative manner by dioxin-like compounds (Pluim et al., 1994; Weisglas-Kuperus et al., 1995; ten Tusscher et al., 2003; Leijs et al., 2009). Based on the findings in humans and in mice (Ackerman et al., 1989) we would postulate that using human lymphocytes for studying the effects of dioxins and dioxin-like compounds in vitro is not correct. Studying the effects on PMNs would be more logical. It must, however, be borne in mind that these cells are produced in
http://dx.doi.org/10.1016/j.toxlet.2014.10.002 0378-4274/ ã 2014 Elsevier Ireland Ltd. All rights reserved.
bone marrow that has been exposed to dioxins for years. Epigenetic changes therefore also need to be considered, as shown in the upregulation of haemoglobin genes in the Seveso population (McHale et al., 2007). The influence of hypoxia must also be taken taken into account (Vorrink et al., 2014). Conflict of interest The authors declare that there are no conflicts of interest. Transparency document The Transparency document associated with this article can be found in the online version. References Ackerman, M.F., Gasiewicz, T.A., Lamm, K.R., Germolec, D.R., Luster, M.I., 1989. Selective inhibition of polymorphonuclear neutrophil activity by 2,3,7,8tetrachlorodibenzo-p-dioxin. Toxicol. Appl. Pharmacol. 101 (3), 470–480. Leijs, M.M., Koppe, J.G., Olie, K., van Aalderen, W.M.C., de Voogt, P., ten Tusscher, G. W., 2009. Effects of dioxins, PCBs and PBDEs on immunology and haematology in adolescents. J. Environ. Sci. Technol. 43, 7646–7951. McHale, C.M., Zhang, L., Hubbard, A.E., Zhao, X., Baccarelli, A., Pesatori, A.C., et al., 2007. Microarray analysis of gene expression in peripheral blood mononuclear cells from dioxin-exposed human subjects. Toxicology 229, 101–113. Pluim, H.J., Koppe, J.G., Olie, K., van der Slikke, J.W., Slot, P.C., van BoxTel, C.J., 1994. Clinical laboratory manifestations of exposure to background levels of dioxins in the perinatal period. Acta Paediatr. 83 (6), 583–587 Jun. Stockinger, B., Veldhoen, M., Hirota, K., 2008. AhR expression and its functional consequences on the Th17 effector T cell subset. Organohal. Compd. 70. ten Tusscher, G.W., Steerenberg, P.A., van Loveren, H., Vos, J.G., von dem Borne, A.E.G. K., Westra, M., et al., 2003. Persistent hematologic and immunologic disturbances in 8-year-Old Dutch children associated with perinatal dioxin exposure. Environ. Health Perspect. 111, 1519–1523. van Ede, K., Gaisch, K.P.J., Van den Berg, M., van Duursen, M.B.M., 2014. Differential relative effect ootencies of some dioxin-like compounds in human peripheral blood lymphocytes and murine splenic cells. Toxicol. Lett. 226, 43–52.
Letter to the Editor / Toxicology Letters 232 (2015) 542–543 Veldhoen, M., Hirota, K., Westendorff, A.M., Buer, J., Dumoutier, L., Renuald, J.C., et al., 2008. The aryl hydrocarbon receptor links Th17-cell-mediated autoimmunity to environmental toxins. Nature 453, 106–109 101038/ nature06881. Vorrink, S.U., Severson, P.L., Kulak, M.V., Futscher, B.W., Domann, F.E., 2014. Hypoxia perturbs aryl hydrocarbon receptor signaling and CYP1A1 expression induced by PCB 126 in human skin and liver-derived cell lines. Toxicol. Appl. Pharmacol. 274, 408–416. Weisglas-Kuperus, N., Sas, T.C.J., Koopman-Esseboom, C., van der Zwan, C.W., de Ridder, M.A.J., Beishuizen, A., et al., 1995. Ímmunologic effects of background prenatal and postnatal exposure to dioxins and polychlorinated biphenyls in Dutch Infants. Pediatr. Res. 38, 404–410.
543
Janna Koppea,* Gavin W. Ten Tusscherb a University of Amsterdam, Emma Children’s Hospital-AMC, Dept. of Pulmonology, Hollandstraat 6, 3634 AT Loenersloot, The Netherlands b
Department of Paediatrics and Neonatology, Westfriesgasthuis, Hoorn, The Netherlands * Corresponding author. Tel.: +31 294291589.