The thymus atrophy-inducing organotin compound DBTC inhibits the binding of thymocytes to thymic epithelial cells.
In this study, it is examined whether the organotin compound di-n-butyltindichloride (DBTC), which has been shown to inhibit immature thymocyte proliferation, is able to disturb the binding between thymocytes and thymic epithelial cells (TEC). To that end, an enzyme-linked binding assay was developed in which the amount of binding of Thy-1+ (mAb ER4)-thymocytes to the rat-derived TEC-line IT45R1 (IT45R1-TEC) could be detected. It was found that preincubation of thymocytes with 3-5 microM DBTC for 30 min inhibited the binding by 50-60% during a 1 h adhesion period. By extending the preincubation period to 1 h and the adhesion period to 22 h, 0.1 microM DBTC was already sufficient to reduce the binding with 60-80%. Further characterization of the binding revealed that splenic lymphocytes were unable to bind to the MHC class II-negative IT45R1-TEC. Since dextran sulfate inhibited the binding as well, sulfated polysaccharide-binding molecules such as Thy-1 and CD2 are likely to be involved in the binding. Electron microscopy showed filament-containing microvilli at the site of interaction. The results are discussed in relation to the mechanism of DBTC-induced thymus atrophy.
Pieters
R H
RH
Research Institute of Toxicology, University of Utrecht, The Netherlands.
Albers
R
R
Bleumink
R
R
Snoeij
N J
NJ
Itoh
T
T
Seinen
W
W
Penninks
A H
AH
D000818:Animals; D001284:Atrophy; D018801:CD2 Antigens / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D003864:Depression, Chemical; D016264:Dextran Sulfate / Q000494:pharmacology; D004848:Epithelium / Q000378:metabolism / Q000648:ultrastructure; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D008854:Microscopy, Electron; D009947:Organotin Compounds / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000378:metabolism; D018800:Thy-1 Antigens / Q000378:metabolism; D013950:Thymus Gland / Q000187:drug effects* / Q000473:pathology
D018801:CD2 Antigens; D000949:Histocompatibility Antigens Class II; D009947:Organotin Compounds; D018800:Thy-1 Antigens; D016264:Dextran Sulfate; C020735:dibutyldichlorotin