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Activation of macrophage cytostatic effector mechanisms during acute graft-versus-host disease: release of intracellular iron and nitric oxide–mediated.

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Presentation on theme: "Activation of macrophage cytostatic effector mechanisms during acute graft-versus-host disease: release of intracellular iron and nitric oxide–mediated."— Presentation transcript:

1 Activation of macrophage cytostatic effector mechanisms during acute graft-versus-host disease: release of intracellular iron and nitric oxide–mediated cytostasis by Frederick P. Nestel, Robert N. Greene, Krikor Kichian, Premysl Ponka, and Wayne S. Lapp Blood Volume 96(5): September 1, 2000 ©2000 by American Society of Hematology

2 LPS dose response for Mφ-mediated release of intracellular iron from target cells during acute GVH.Target cell release of 59Fe (○) and 51Cr (▵) mediated by Mφ from normal B6AF1 mice and release of 59Fe (●) and 51Cr (▴) mediated by Mφ from acute GVHD B6AF1 m... LPS dose response for Mφ-mediated release of intracellular iron from target cells during acute GVH.Target cell release of 59Fe (○) and 51Cr (▵) mediated by Mφ from normal B6AF1 mice and release of 59Fe (●) and 51Cr (▴) mediated by Mφ from acute GVHD B6AF1 mice transplanted 14 days previously with 60 × 106 B6 cells. Mφ-mediated radioisotope release was determined using 59Fe,51Cr dual-labeled MDW4 cells in an 18-hour assay as described in “Materials and methods.” Each value represents the mean ± SD of 4 replicates of pooled Mφ effector cells. Similar results were obtained in 2 separate experiments. Frederick P. Nestel et al. Blood 2000;96: ©2000 by American Society of Hematology

3 NMMA inhibits NO production and cytostatic activity mediated by acute GVHD-primed, LPS-triggered Mφ.Acute GVHD Mφ (▪) from B6AF1 animals transplanted 14 days previously with 60 × 106 B6 cells were activated with 2.5 ng/mL LPS, and normal Mφ (■) from B6AF1an... NMMA inhibits NO production and cytostatic activity mediated by acute GVHD-primed, LPS-triggered Mφ.Acute GVHD Mφ (▪) from B6AF1 animals transplanted 14 days previously with 60 × 106 B6 cells were activated with 2.5 ng/mL LPS, and normal Mφ (■) from B6AF1animals were activated with 2.5 ng/mL LPS and IFN-γ. (A) The concentration of NO in 48-hour culture supernatants was determined as described in “Materials and methods.” Mφ were cultured in phenol red–free RPMI 1640 containing 1.0 mmol/L L-arginine plus 10% FCS with or without NMMA as indicated. Results represent the mean ± SD of triplicates. Similar results were obtained in 2 separate experiments. (B) Mφ-mediated cytostasis of MDW4 cells was determined as described in “Materials and methods.” Mφ and targets were cultured for 48 hours in RPMI 1640 plus 10% FCS containing 1.0 mmol/L L-arginine either with or without NMMA as indicated. Results represent the mean ± SEM of 3 experiments. Frederick P. Nestel et al. Blood 2000;96: ©2000 by American Society of Hematology


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