R. Near, R. Matulka, K. Mann, S. Gogate, A. Trombino, D. Sherr
{"title":"Regulation of preB cell apoptosis by aryl hydrocarbon receptor/transcription factor-expressing stromal/adherent cells.","authors":"R. Near, R. Matulka, K. Mann, S. Gogate, A. Trombino, D. Sherr","doi":"10.1046/j.1525-1373.1999.d01-82.x","DOIUrl":null,"url":null,"abstract":"Polycyclic aromatic hydrocarbons (PAH) are environmental chemicals that mediate immunosuppression. In long-term bone marrow B-cell lymphopoiesis models, PAH induce apoptosis in immature (preB) lymphocytes. Since the biologic function of PAH is often mediated by the aryl hydrocarbon receptor/transcription factor (AhR), the role of the AhR or AhR-regulated genes was assessed in preB cell apoptosis. Specifically, a bone marrow-derived preB cell line (BU-11) was cultured on monolayers of the AhR + bone marrow-derived stromal cell line BMS2, hepatoma sublines that express various levels of AhR activity (Hepa-1c1c7 and variants), AhR+ thymic epithelial cells, and primary bone marrow stromal cells from wildtype or AhR-/- mice. Cultures were treated with one of two prototypic PAH, 7,12-dimethylbenz[a] anthracene (DMBA) or benz[a]pyrene (B[a]P), and the percentage of cells undergoing apoptosis measured. The data demonstrated that: 1) bone marrow- and hepatic-derived stromal/adherent cells support preB cell growth and regulate apoptosis induced by DMBA or B[a]P; 2) B[a]P is more effective than DMBA when preB cells are maintained on Hepa-1c1c7 monolayers than when maintained on BMS2 monolayers; 3) DMBA is more effective than B[a]P when preB cells are cultured on BMS2 monolayers; 4) alpha-naphthoflavone, an AhR antagonist and cytochrome P-450 inhibitor, blocks preB cell apoptosis in both BU-11/Hepa-1c1c7 and BU-11/BMS2 cultures; 5) although preB cells grow well in Hepa-1c1c7 or BMS2 supernatants, addition of PAH in the absence of hepatic- or bone marrow-derived adherent cells does not result in preB cell apoptosis; 6) preB cell apoptosis is dependent on AhR activity in adherent hepatic- or bone marrow-derived stromal cells; and 7) apoptosis is induced by DMBA when preB cells are maintained on primary bone marrow stromal cell monolayers from wildtype but not from AhR-/- mice. Collectively, the data indicated that AhR-regulated activities in the hematopoietic microenvironment influence the susceptibility of immature lymphocytes to low-dose PAH exposure.","PeriodicalId":20618,"journal":{"name":"Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine","volume":"40 1","pages":"242-52"},"PeriodicalIF":0.0000,"publicationDate":"1999-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"28","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1046/j.1525-1373.1999.d01-82.x","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 28
Abstract
Polycyclic aromatic hydrocarbons (PAH) are environmental chemicals that mediate immunosuppression. In long-term bone marrow B-cell lymphopoiesis models, PAH induce apoptosis in immature (preB) lymphocytes. Since the biologic function of PAH is often mediated by the aryl hydrocarbon receptor/transcription factor (AhR), the role of the AhR or AhR-regulated genes was assessed in preB cell apoptosis. Specifically, a bone marrow-derived preB cell line (BU-11) was cultured on monolayers of the AhR + bone marrow-derived stromal cell line BMS2, hepatoma sublines that express various levels of AhR activity (Hepa-1c1c7 and variants), AhR+ thymic epithelial cells, and primary bone marrow stromal cells from wildtype or AhR-/- mice. Cultures were treated with one of two prototypic PAH, 7,12-dimethylbenz[a] anthracene (DMBA) or benz[a]pyrene (B[a]P), and the percentage of cells undergoing apoptosis measured. The data demonstrated that: 1) bone marrow- and hepatic-derived stromal/adherent cells support preB cell growth and regulate apoptosis induced by DMBA or B[a]P; 2) B[a]P is more effective than DMBA when preB cells are maintained on Hepa-1c1c7 monolayers than when maintained on BMS2 monolayers; 3) DMBA is more effective than B[a]P when preB cells are cultured on BMS2 monolayers; 4) alpha-naphthoflavone, an AhR antagonist and cytochrome P-450 inhibitor, blocks preB cell apoptosis in both BU-11/Hepa-1c1c7 and BU-11/BMS2 cultures; 5) although preB cells grow well in Hepa-1c1c7 or BMS2 supernatants, addition of PAH in the absence of hepatic- or bone marrow-derived adherent cells does not result in preB cell apoptosis; 6) preB cell apoptosis is dependent on AhR activity in adherent hepatic- or bone marrow-derived stromal cells; and 7) apoptosis is induced by DMBA when preB cells are maintained on primary bone marrow stromal cell monolayers from wildtype but not from AhR-/- mice. Collectively, the data indicated that AhR-regulated activities in the hematopoietic microenvironment influence the susceptibility of immature lymphocytes to low-dose PAH exposure.