Cellular and molecular aspects of organotin-induced thymus atrophy.
1. Organotin compounds, di-n-butyltin dichloride (DBTC) in particular, have been shown to cause thymus atrophy in the rat. 2. DBTC-induced thymus atrophy results from a depletion of small CD4+CD8+ thymocytes which is caused by a diminished production of immature CD4-CD8+ and CD4+CD8+ thymoblasts. 3. DBTC inhibits the activation, but not the differentiation of immature CD4-CD8+ thymocytes in vitro and in vivo suggesting a selective antiproliferative activity of DBTC. 4. DBTC inhibits the adhesion molecule-mediated binding of thymocytes to thymic epithelial cells. 5. DBTC enhances the Ca2+ release elicited by cross-linking of the T cell receptor complex (TcR alpha beta-CD3) on thymocytes and moreover delays cap formation of the TcR alpha beta-CD3 receptor. 6. It is concluded that DBTC possibly interferes with the functioning of the cytoskeleton. The relation of the in vitro findings to the inhibition of immature CD4-CD8+ thymocyte activation and the induction of thymus atrophy is unknown as yet.
Pieters
R H
RH
Research Institute of Toxicology, Utrecht University, The Netherlands.
Bol
M
M
Seinen
W
W
Penninks
A H
AH
D000818:Animals; D001284:Atrophy; D001665:Binding Sites; D016516:CD4-CD8 Ratio / Q000187:drug effects*; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D009947:Organotin Compounds / Q000633:toxicity*; D051381:Rats; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013950:Thymus Gland / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D009947:Organotin Compounds; D017260:Receptor-CD3 Complex, Antigen, T-Cell; C020735:dibutyldichlorotin