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Anastasia Nijnik - One of the best experts on this subject based on the ideXlab platform.
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the role of sphingosine 1 phosphate transporter spns2 in Immune System Function
Journal of Immunology, 2012Co-Authors: Anastasia Nijnik, Simon Clare, Christine Hale, Jing Chen, Claire Raisen, Lynda Mottram, Mark Lucas, Jeanne Estabel, Edward RyderAbstract:Sphingosine-1-phosphate (S1P) is lipid messenger involved in the regulation of embryonic development, Immune System Functions, and many other physiological processes. However, the mechanisms of S1P transport across cellular membranes remain poorly understood, with several ATP-binding cassette family members and the spinster 2 (Spns2) member of the major facilitator superfamily known to mediate S1P transport in cell culture. Spns2 was also shown to control S1P activities in zebrafish in vivo and to play a critical role in zebrafish cardiovascular development. However, the in vivo roles of Spns2 in mammals and its involvement in the different S1P-dependent physiological processes have not been investigated. In this study, we characterized Spns2 -null mouse line carrying the Spns2 tm1a(KOMP)Wtsi allele ( Spns2 tm1a ). The Spns2 tm1a/tm1a animals were viable, indicating a divergence in Spns2 Function from its zebrafish ortholog. However, the immunological phenotype of the Spns2 tm1a/tm1a mice closely mimicked the phenotypes of partial S1P deficiency and impaired S1P-dependent lymphocyte trafficking, with a depletion of lymphocytes in circulation, an increase in mature single-positive T cells in the thymus, and a selective reduction in mature B cells in the spleen and bone marrow. Spns2 activity in the nonhematopoietic cells was critical for normal lymphocyte development and localization. Overall, Spns2 tm1a/tm1a resulted in impaired humoral Immune responses to immunization. This study thus demonstrated a physiological role for Spns2 in mammalian Immune System Functions but not in cardiovascular development. Other components of the S1P signaling network are investigated as drug targets for immunosuppressive therapy, but the selective action of Spns2 may present an advantage in this regard.
Robert L Lochmiller - One of the best experts on this subject based on the ideXlab platform.
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sensitivity of a standard host resistance assay using streptococcus agalactiae for assessing exposure to immunotoxicants in wild cotton rats sigmodon hispidus
Archives of Environmental Contamination and Toxicology, 2000Co-Authors: L C Jones, Robert L Lochmiller, J A Sinclair, R H MortonAbstract:Resident small mammals have been used for in situ biomonitoring of contaminated waste sites containing suspected immunotoxicants. Host resistance assays, which involve challenging animals with an actual pathogen, allow for testing of overall Immune System Function in animals. Because such assays have not been evaluated for use with wild rodent species, it was our objective to assess the efficacy of Streptococcus agalactiae as a pathogenic model for use in a host resistance assay for detecting alterations in Immune System Function in wild cotton rats (Sigmodon hispidus). The ability of the assay to detect immunosuppression was evaluated by inducing immunosuppression chemically (cyclophosphamide or dexamethasone) and by protein malnutrition. The estimated lethal dose of S. agalactiae that killed 50% of challenged animals (LD 50 ) was 5.76 X 10 7 colony-forming units (CFUs). Although bacterial agglutination titers indicated that animals developed an antibody response when immunized, immunization was not sufficient to adequately protect animals from a subsequent pathogenic challenge. Sensitivity of the host resistance assay was only suitable for detecting substantial immunosuppression, such as that induced by protein malnutrition or dexamethasone administration.
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selected Immune responses of adult cotton rats sigmodon hispidus to dietary restriction
Comparative Biochemistry and Physiology Part A: Physiology, 1993Co-Authors: Robert L Lochmiller, Michelle R Vestey, Scott T McmurryAbstract:Abstract 1. 1. We examined the influence of moderate to severe dietary restriction on Immune System Function in adult cotton rats. Animals (N = 80) were fed ad lib. (controls) or restricted [moderate = 80% ad lib. for 1 or 2 weeks; severe = 80% ad lib. for 1 or 2 weeks followed by 40% ad lib. for one (week 3) or two (week 4) additional weeks] amounts of food for 1–4 weeks. 2. 2. Average body weight loss for severely restricted animals in week 4 was 17%; dietary treatments had no measurable effect on hematological parameters (hematocrit, white blood cell count), lymphoid organ weights (thymus gland, spleen, popliteal lymph nodes), and mononuclear cell yields from lymphoid organs. 3. 3. Cell-mediated Immune Function was assessed in vitro by a lymphoproliferative response assay and in vivo by a delayed-type hypersensitivity response assay. 4. 4. Proliferative responses of spleen cell cultures stimulated with concanavalin A (Con A, Canavalia ensiformis) and pokeweed (PWM, Phytolacca americana) were normal or significantly greater among moderately restricted than control cotton rats during week 1 and week 2. 5. 5. Lymphoproliferative responses of severely restricted animals were normal or reduced during week 3 and week 4. 6. 6. Delayed-type hypersensitivity responses to the contact antigen oxazolone were significantly depressed among severely restricted animals in week 4 compared to controls. 7. 7. In comparison with laboratory rodent strains, our initial results indicate that Immune System Function in adult cotton rats is not as sensitive to short term (1–4 weeks) periods of dietary restriction. 8. 8. Immune System Function was related to changes in body weight as a result of feed restriction.
Scott T Mcmurry - One of the best experts on this subject based on the ideXlab platform.
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selected Immune responses of adult cotton rats sigmodon hispidus to dietary restriction
Comparative Biochemistry and Physiology Part A: Physiology, 1993Co-Authors: Robert L Lochmiller, Michelle R Vestey, Scott T McmurryAbstract:Abstract 1. 1. We examined the influence of moderate to severe dietary restriction on Immune System Function in adult cotton rats. Animals (N = 80) were fed ad lib. (controls) or restricted [moderate = 80% ad lib. for 1 or 2 weeks; severe = 80% ad lib. for 1 or 2 weeks followed by 40% ad lib. for one (week 3) or two (week 4) additional weeks] amounts of food for 1–4 weeks. 2. 2. Average body weight loss for severely restricted animals in week 4 was 17%; dietary treatments had no measurable effect on hematological parameters (hematocrit, white blood cell count), lymphoid organ weights (thymus gland, spleen, popliteal lymph nodes), and mononuclear cell yields from lymphoid organs. 3. 3. Cell-mediated Immune Function was assessed in vitro by a lymphoproliferative response assay and in vivo by a delayed-type hypersensitivity response assay. 4. 4. Proliferative responses of spleen cell cultures stimulated with concanavalin A (Con A, Canavalia ensiformis) and pokeweed (PWM, Phytolacca americana) were normal or significantly greater among moderately restricted than control cotton rats during week 1 and week 2. 5. 5. Lymphoproliferative responses of severely restricted animals were normal or reduced during week 3 and week 4. 6. 6. Delayed-type hypersensitivity responses to the contact antigen oxazolone were significantly depressed among severely restricted animals in week 4 compared to controls. 7. 7. In comparison with laboratory rodent strains, our initial results indicate that Immune System Function in adult cotton rats is not as sensitive to short term (1–4 weeks) periods of dietary restriction. 8. 8. Immune System Function was related to changes in body weight as a result of feed restriction.
Edward Ryder - One of the best experts on this subject based on the ideXlab platform.
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the role of sphingosine 1 phosphate transporter spns2 in Immune System Function
Journal of Immunology, 2012Co-Authors: Anastasia Nijnik, Simon Clare, Christine Hale, Jing Chen, Claire Raisen, Lynda Mottram, Mark Lucas, Jeanne Estabel, Edward RyderAbstract:Sphingosine-1-phosphate (S1P) is lipid messenger involved in the regulation of embryonic development, Immune System Functions, and many other physiological processes. However, the mechanisms of S1P transport across cellular membranes remain poorly understood, with several ATP-binding cassette family members and the spinster 2 (Spns2) member of the major facilitator superfamily known to mediate S1P transport in cell culture. Spns2 was also shown to control S1P activities in zebrafish in vivo and to play a critical role in zebrafish cardiovascular development. However, the in vivo roles of Spns2 in mammals and its involvement in the different S1P-dependent physiological processes have not been investigated. In this study, we characterized Spns2 -null mouse line carrying the Spns2 tm1a(KOMP)Wtsi allele ( Spns2 tm1a ). The Spns2 tm1a/tm1a animals were viable, indicating a divergence in Spns2 Function from its zebrafish ortholog. However, the immunological phenotype of the Spns2 tm1a/tm1a mice closely mimicked the phenotypes of partial S1P deficiency and impaired S1P-dependent lymphocyte trafficking, with a depletion of lymphocytes in circulation, an increase in mature single-positive T cells in the thymus, and a selective reduction in mature B cells in the spleen and bone marrow. Spns2 activity in the nonhematopoietic cells was critical for normal lymphocyte development and localization. Overall, Spns2 tm1a/tm1a resulted in impaired humoral Immune responses to immunization. This study thus demonstrated a physiological role for Spns2 in mammalian Immune System Functions but not in cardiovascular development. Other components of the S1P signaling network are investigated as drug targets for immunosuppressive therapy, but the selective action of Spns2 may present an advantage in this regard.
Ronald N Germain - One of the best experts on this subject based on the ideXlab platform.
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seeing is believing a focus on the contribution of microscopic imaging to our understanding of Immune System Function
European Journal of Immunology, 2007Co-Authors: Marc Bajenoff, Ronald N GermainAbstract:Many cells of the Immune System do not occupy fixed tissue locations, but circulate in the blood, traffic through the lymph, and migrate within organized lymphoid organs and periphery tissues. Rare antigen-specific lymphocytes must find one another for productive adaptive Immune responses and the different phases of cell-mediated and humoral Immune response development take place in distinct sites. This historical feature examines how we have reached our current understanding of these aspects of Immune System Function. It emphasizes the critical role of ever-improving imaging techniques in determining where Immune cells reside and interact and stresses the key past contribution of sequential static immunohistochemical analysis using monoclonal reagents. In combination with genetic studies, these imaging experiments resulted in our current paradigm that views activation-dependent changes in chemokine sensitivity as central to effective cell co-operation. We also highlight the very recent application of two-photon imaging to the direct observation of Immune cell dynamics in a natural tissue environment, noting how the application of this technology has reinforced some existing ideas and is changing other long-held views. We conclude with some speculations about the opportunities for further advances using ever more powerful imaging methods.
