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From the Cover: Tributyltin Alters the Bone Marrow Microenvironment and Suppresses B Cell Development
- Source :
- Toxicological Sciences. 158:63-75
- Publication Year :
- 2017
- Publisher :
- Oxford University Press (OUP), 2017.
-
Abstract
- Organotins are industrial chemicals and agricultural pesticides, and they contaminate both outdoor and indoor environments. Organotins are detectable in human sera at biologically active concentrations and are immuno-and neuro-toxicants. Triphenyltin, tributyltin (TBT) and dibutyltin activate peroxisome proliferator-activated receptor γ in bone marrow multipotent mesenchymal stromal cells and promote adipogenesis. TBT also has been shown to suppress osteogenesis; osteoblasts not only support bone homeostasis but also support B lymphopoiesis. In addition, developing B cells are highly sensitive to exogenous insults. Thus, we hypothesized that bone marrow B cells may be negatively affected by TBT exposure both directly, through activation of apoptosis, and indirectly, through alterations of the bone marrow microenvironment. TBT activated apoptosis in developing B cells at environmentally relevant concentrations (as low as 80 nM) in vitro, via a mechanism that is distinct from that induced by high dose (μM) TBT and that requires p53. TBT suppressed the proliferation of hematopoietic cells in an ex vivo bone marrow model. Concurrent treatment of stromal cells and B cells or pretreatment of stromal cells with TBT induced adipogenesis in the stromal cells and reduced the progression of B cells from the early pro B (Hardy fraction B) to the pre B stage (Hardy fraction D). In vivo, TBT induced adipogenesis in bone marrow, reduced "aging-sensitive" AA4+CD19+ B cells in bone marrow, and reduced splenic B cell numbers. Immunosenescence and osteoporosis are adverse health effects of aging, we postulate that TBT exposure may mimic, and possibly intensify, these pathologies.
- Subjects :
- 0301 basic medicine
Stromal cell
Apoptosis
Biology
Toxicology
CD19
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Suppression of B Cell Development by Tributyltine
Bone Marrow
medicine
Animals
Homeostasis
Humans
Lymphopoiesis
B cell
B-Lymphocytes
Adipogenesis
Dose-Response Relationship, Drug
Mesenchymal Stem Cells
3. Good health
Cell biology
Mice, Inbred C57BL
Haematopoiesis
030104 developmental biology
medicine.anatomical_structure
chemistry
Immunology
biology.protein
Tributyltin
Bone marrow
Trialkyltin Compounds
030215 immunology
Subjects
Details
- ISSN :
- 10960929 and 10966080
- Volume :
- 158
- Database :
- OpenAIRE
- Journal :
- Toxicological Sciences
- Accession number :
- edsair.doi.dedup.....d363161f2cf8fbc15e805b0eef0cc030