Ceacam1 separates graft-versus-host-disease from graft-versus-tumor activity after experimental allogeneic bone marrow transplantation.

BACKGROUND: Allogeneic bone marrow transplantation (allo-BMT) is a potentially curative therapy for a variety of hematologic diseases, but benefits, including graft-versus-tumor (GVT) activity are limited by graft-versus-host-disease (GVHD). Carcinoembryonic antigen related cell adhesion molecule 1 (Ceacam1) is a transmembrane glycoprotein found on epithelium, T cells, and many tumors. It regulates a variety of physiologic and pathological processes such as tumor biology, leukocyte activation, and energy homeostasis. Previous studies suggest that Ceacam1 negatively regulates inflammation in inflammatory bowel disease models. METHODS: We studied Ceacam1 as a regulator of GVHD and GVT after allogeneic bone marrow transplantation (allo-BMT) in mouse models. In vivo, Ceacam1(-/-) T cells caused increased GVHD mortality and GVHD of the colon, and greater numbers of donor T cells were positive for activation markers (CD25(hi), CD62L(lo)). Additionally, Ceacam1(-/-) CD8 T cells had greater expression of the gut-trafficking integrin α(4)β(7), though both CD4 and CD8 T cells were found increased numbers in the gut post-transplant. Ceacam1(-/-) recipients also experienced increased GVHD mortality and GVHD of the colon, and alloreactive T cells displayed increased activation. Additionally, Ceacam1(-/-) mice had increased mortality and decreased numbers of regenerating small intestinal crypts upon radiation exposure. Conversely, Ceacam1-overexpressing T cells caused attenuated target-organ and systemic GVHD, which correlated with decreased donor T cell numbers in target tissues, and mortality. Finally, graft-versus-tumor survival in a Ceacam1(+) lymphoma model was improved in animals receiving Ceacam1(-/-) vs. control T cells. CONCLUSIONS: We conclude that Ceacam1 regulates T cell activation, GVHD target organ damage, and numbers of donor T cells in lymphoid organs and GVHD target tissues. In recipients of allo-BMT, Ceacam1 may also regulate tissue radiosensitivity. Because of its expression on both the donor graft and host tissues, this suggests that targeting Ceacam1 may represent a potent strategy for the regulation of GVHD and GVT after allogeneic transplantation

Effects of carbofuran and metsulfuron-methyl on the benthic macroinvertebrate community in flooded ricefields Efeito do carbofurano e metsulfuron-methyl sobre a comunidade de macroinvertebrados bentônicos de lavoura de arroz irrigado

AIM: This study evaluated the effect of the insecticide carbofuran and the herbicide metsulfuron-methyl on the abundance and diversity of benthic macroinvertebrates in a paddy ricefield. METHODS: To achieve this goal, two pesticide treatments [the insecticide carbofuran (IC) and the herbicide metsulfuron-methyl (HM)] and a control (Co) treatment with no added pesticide were established in an experimental area of the Plant Science Department of the Federal University of Santa Maria. Soil samples were collected in triplicate from each treatment 30 days before and 1, 10, and 51 days after the pesticide application, for macrofauna identification. RESULTS: Among the 21 taxa identified, Trichoceridae was present only in Co, Hydroptilidae was recorded only in IC, and Corixidae in HM. In Co, the most abundant group was Annelida, while in IC and HM Diptera (Chironomidae) was dominant. Significant differences were observed between Co and IC, in the density of Odontoceridae (Control>IC) and Hydrophilidae (Control<IC), and between Co and HM in the density of Odontoceridae (Control>HM) and Hirudinea (Control<HM). CONCLUSION: In spite of the possible negative effects of the pesticides on the benthic community, the assemblages recovered rapidly.<br>OBJETIVO: O objetivo desse estudo foi avaliar o efeito do inseticida carbofurano e do herbicida metsulfuron-methyl na abundância e diversidade de macroinvertebrados bentônicos em campo de arroz irrigado. MÉTODOS: Para isto, dois tratamentos com agrotóxicos [o inseticida carbofurano (IC) e o herbicida metsulfuron-methyl (HM)] e um controle (Co), tratamento sem pesticida, foram aplicados em uma área experimental no Departamento de Fitotecnia da Universidade Federal de Santa Maria. Amostras de solo foram coletadas em triplicatas em cada tratamento 30 dias antes (DBA) e 1, 10 e 51 dias após a aplicação dos pesticidas, posteriormente a macrofauna foi identificada. RESULTADOS: Vinte e um (21) taxa foram identificados, entre esses Trichoceridae esteve presente apenas em Co, enquanto que Hydroptilidae foi coletado apenas em IC, e Corixidae em HM. Em Co e IC, o grupo mais abundante foi Annelida, e em HM foi Diptera (Chironomidae) que prevaleceu. Diferenças significativas foram observadas entre Co e IC, na densidade de Odontoceridae (Co>IC) e Hydrophilidae (Co<IC), e entre Co e HM na densidade de Odontoceridae (Co>HM) e Hirudinea (Co<HM). CONCLUSÃO: Entretanto, apesar dos possíveis efeitos negativos dos pesticidas sobre a comunidade bentônica verificados nos primeiros dias após a aplicação, verificou-se que de forma geral a comunidade recuperou-se rapidamente

Differential Responses of Biochemical and Behavioral Parameters in the Native Gastropod Chilina gibbosa Exposed Subchronically to Environmental Concentrations of Two Insecticides Used in Argentina

In this chapter, we show the results obtained after exposing the freshwater gastropod Chilina gibbosa 7 and 14 days to the organophosphate azinphos-methyl and the carbamate carbaryl. These insecticides are applied in Argentina and found in water bodies. Chilina gibbosa is naturally distributed in our country, and the family (Chilinidae) is considered vulnerable. It has an important role in the ecosystem being food of fishes and birds. After exposure to the same molar concentration of these insecticides, which corresponds to an environmental concentration in both cases, we registered lethality, neurotoxicity, and cholinesterase and carboxylesterase activities. Our results show that the subchronic exposure to an environmental concentration of azinphos-methyl caused severe signs of neurotoxicity (the abnormal exposure of the head-foot region and the loss of adherence) after 7 and 14 days of exposure. Cholinesterases were more sensitive than carboxylesterases. Inhibition of 89% of cholinesterase activity was observed after 7 days of exposure, while the decrease of carboxylesterase activity occurred after 14 days. Additionally, azinphos-methyl decreased protein content in C. gibbosa. On the other hand, the subchronic exposure to carbaryl only produced an inhibition of carboxylesterase activity measured with p-nitrophenyl butyrate as substrate. We conclude that insecticides applied in Argentina can cause toxic effects in the native gastropod C. gibbosa and that azinphos-methyl is more toxic than carbaryl. The presence of these insecticides in water bodies could put this species at risk, negatively disturbing the environment.Fil: Boburg Castroconde, Beverly. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Herbert, Lucila Thomsett. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Cossi, Paula Fanny. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Kristoff, Gisela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentin