Background β-thalassemia occurs from the imbalanced globin chain synthesis due to the absence or inadequate β-globin chain production. The excessive unbound α-globin chains precipitate in erythroid precursors and mature red blood cells leading to ineffective erythropoiesis and hemolysis. Design and MethodsIn vitro globin chain synthesis in reticulocytes from different types of thalassemic mice was performed. The effect of imbalanced globin chain synthesis was assessed from changes of red blood cell properties including increased numbers of red blood cells vesicles and apoptotic red blood cells, increased reactive oxygen species and decreased red blood cell survival. ResultsThe α/β-globin chain ratio in β -thalassemic mice, 1.26±0.03, was significantly higher than that of wild type mice, 0.96±0.05. The thalassemic mice show abnormal hematologic data and defective red blood cell properties. These values were improved significantly in doubly heterozygous thalassemic mice harboring 4 copies of human β E -globin transgene, with a more balanced globin chain synthesis, 0.92±0.05. Moreover, transgenic mice harboring 8 extra copies of the human β E -globin transgene showed inversely imbalanced α/β-globin synthesis ratio, 0.83±0.01, that resulted in a mild β-thalassemia phenotype due to the excessive β-globin chains. The degree of ineffective erythropoiesis also correlated with the degree of imbalanced globin chain synthesis. Bone marrow and splenic erythroid precursor cells of β -thalassemic mice showed increased phosphatidylserine exposure in basophilic and polychromatophilic stages, which was restored to the normal level in doubly heterozygous mice. ConclusionsImbalanced α/β-globin chain as a consequence of either reduction or enhancement of β-globin chain synthesis can cause abnormal red blood cell properties in mouse models.Key words: thalassemia, transgenic mice, ineffective erythropoiesis, globin chain synthesis. mice. Haematologica 2009;94:1211-1219. doi:10.3324/haematol.2009 This is an open-access paper. Citation: Srinoun K, Svasti S, Chumworathayee W, Vadolas J, Vattanaviboon P, Fucharoen S, and Winichagoon P. Imbalanced globin chain synthesis determines erythroid cell pathology in thalassemic Imbalanced globin chain synthesis determines erythroid cell pathology in thalassemic mice
Bacterial communication system known as quorum-sensing (QS) is a pivotal system for bacterial survival, adaptation and pathogenesis. Members in the multicellular community may synthesize or acquire a signaling molecule in order to elicit downstream cellular processes. Roles of indole and derivatives, a new class of quorum-sensing signal molecules, in various bacterial physiologies and virulence have been reported recently. Indole is normally found in mammal gastrointestinal tract as a metabolite of tryptophan metabolism by microbiota. Therefore, interspecies connection via indole signaling among commensal bacteria and enteric pathogens could be anticipated. Effects of indole exposure on the virulence of Listeria monocytogenes were investigated by phenotypic and molecular approaches. Results demonstrated that synthetic indole and indole-rich conditioned medium significantly diminished biofilm formation and related virulence of L. monocytogenes including motility, cell aggregation and exopolysaccharide (EPS) production. Transcript levels of virulence-associated (pssE, dltA, flaA, fliI, motB, agrA and hly) and regulatory-genes (codY, sigB, prfA and gmaR) were substantially down-regulated in indole-treated cells. Only mogR gene encoding for a repressor of motility genes was up-regulated after indole exposure. Our findings raise the possibility that L. monocytogenes may acquire indole signaling from gut microbiota for resource-effective adaptation upon transition to new environment.
Abnormal red blood cell (RBC) clearance in β-thalassemia is triggered by activated monocytes. Recent reports indicate that miRNA (miR-) plays a role in monocyte activation. To study phagocytic function, we co-cultured monocytes of normal, non-splenectomized and splenectomized β-thalassemia/HbE individuals with RBCs obtained from normal, non-splenectomized and splenectomized β-thalassemia/HbE individuals. The phagocytic activity of β-thalassemia/HbE monocytes co-cultured with β-thalassemia/HbE RBCs was significantly higher than that of normal monocytes co-cultured with normal RBCs. Upregulation of monocyte miR-155 was observed in β-thalassemia/HbE patients. Increased miR-155 was associated with reductions in BTB and CNC Homology1 (BACH1) target gene expression and increased phagocytic activity of β-thalassemia/HbE monocytes. Taken together, these findings suggested that increased miR-155 expression in activated monocytes leads to enhanced phagocytic activity via BACH-1 regulation in β-thalassemia/HbE. This provides novel insights into the phagocytic clearance of abnormal RBCs in β-thalassemia/HbE.
Automated hematology instruments originally developed for human laboratories have been established for veterinary species. 1-6 The Mindray BC-5000Vet hematology system (Mindray) was recently released. This software was developed for the analysis of blood from 13 animal species, including dog, cat, horse, monkey, ferret, rat, mouse, rabbit, pig, cow, donkey, goat, and sheep. The Mindray BC-5000Vet is an automated hematology system providing 23 parameters including red blood cell (RBC) and platelet counts, hemoglobin (HGB) concentrations, white blood cell (WBC) counts, and a 5-part differential WBC analysis. In previous studies, the Advia 2120, Advia 120, Sysmex XT-2000iV, and Sysmex F-800 semi-automated hematology analyzers were validated in canine and feline blood with samples from both healthy and sick animals. 1-7 However, the Mindray BC-5000Vet
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