The thymus atrophy inducing organotin compound DBTC stimulates TcR alpha beta-CD3 signalling in immature rat thymocytes.
In the present study, we show that the thymus atrophy inducing compound DBTC stimulates the intracellular release, but not the influx, of Ca2+ elicited by cross-linking of the TcR alpha beta-CD3-complex on rat thymocytes and inhibits capping of TcR alpha beta. Similarities with the effects of cytochalasin B together with the finding that DBTC also inhibited capping of CD8, whereas cross-linking of CD8 did not cause a Ca(2+)-response, suggest that DBTC interferes with TcR alpha beta-CD3-signalling by selective interference with cytoskeletal functioning. The responding thymocytes were CD53- and FSClow, thus possibly including the non proliferating counterpart of the presumed immature CD4-CD8+CD53-target cells of DBTC. The present effects may therefore relate to the mechanisms of organotin-induced thymus atrophy.
Pieters
R H
RH
Research Institute of Toxicology, Utrecht University, The Netherlands.
Punt
P
P
Bol
M
M
van Dijken
J M
JM
Seinen
W
W
Penninks
A H
AH
D000818:Animals; D001386:Azides / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003571:Cytochalasin B / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009947:Organotin Compounds / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000502:physiology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology*; D015398:Signal Transduction; D019810:Sodium Azide; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013723:Teratogens / Q000494:pharmacology*; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology / Q000473:pathology*
D001386:Azides; D009947:Organotin Compounds; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013723:Teratogens; D003571:Cytochalasin B; D019810:Sodium Azide; C020735:dibutyldichlorotin; D002118:Calcium