Differential effect of cyclosporin application on epithelial cells of the rat thymus. Immunohistochemical study

Milićević, Živana; Živanović, Vedran; Todorović, Jovan; Čolić, Miodrag; Kamperdijk, E. W. A.; Heofsmit, E.C.M.; Milićević, Novica M.

doi:10.1016/0021-9975(92)90065-3

Cited by 10 publications

(11 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Their findings were confirmed by Gaudecker (1991). However, using anti-cytokeratin antibodies it is possible to distinguish additional subsets of thymic epithelial cells: in the medulla there are more than just two , 1990Milićević et al 1992). Light-microscopic immunophenotyping, using different monoclonal antibodies, has also documented the heterogeneity of epithelial cells in mouse, human and rat thymus, distinguishing between subcapsular, cortical and medullary areas (van Vliet et al 1984;De Maagd et al 1985;Kampinga et al 1987).…”

Section: Introductionmentioning

confidence: 90%

“…Light-microscopic immunophenotyping, using different monoclonal antibodies, has also documented the heterogeneity of epithelial cells in mouse, human and rat thymus, distinguishing between subcapsular, cortical and medullary areas (van Vliet et al 1984;De Maagd et al 1985;Kampinga et al 1987). However, many of the monoclonals directed against different epitopes expressed on medullary epithelial cells (Farr and Anderson 1985;Rouse et al 1988), including the already-mentioned anti-cytokeratin antibodies , 1990Milićević et al 1992), in different patterns stain only a proportion of these cells in the thymic medulla. Especially often, the antibodies against thymic hormones do not react with all of them (Jambon et al 1981;Savino et al 1982;Gaudecker et al 1986).…”

Section: Introductionmentioning

confidence: 99%

“…In earlier studies attention was focused on the effects of CS on the thymic lymphocyte population, whereas the changes of thymic nonlymphoid cells were neglected. Therefore, we performed a series of experiments to show that thymic macrophages (Milićević et al 1989(Milićević et al , 1993(Milićević et al , 1994, as well as all subsets of thymic epithelial cells (Milićević et al 1991(Milićević et al , 1992, were markedly affected by application of CS. Thus, this agent appeared to be a useful tool for analyzing morphofunctional features of thymic nonlymphoid cells in vivo.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Ultrastructure of different types of thymic epithelial cells in normal and cyclosporin-A-treated rats

Milićević¹,

Milićević²

1997

Anatomy and Embryology

View full text Add to dashboard Cite

Transmission electron microscopy was used to study the ultrastructural features of thymic epithelial cells of intact and cyclosporin-A-treated adult male Wistar rats. The animals received a peroral daily dose of 30 mg of cyclosporin A per kg body weight for 21 consecutive days. On the basis of ultrastructural features, seven subsets of epithelial cells were distinguished within the intact rat thymus. Four subsets were predominantly situated in the cortex (type 4 - "dark" cells - occasionally penetrated into the medullar region) and three were positioned within the thymic medulla. All subsets of thymic epithelial cells were markedly changed after the application of cyclosporin A. The prominent enlargement of cytokeratin contents was registered in type 1 - "subcapsular/paraseptal/perivascular" - epithelial cells. At the same time these cells acquired the morpho-functional aspect of resting cells. All other subsets of cortical epithelial cells were enlarged (though in different ways) in comparison to the corresponding subsets of the control thymus, whereby their subcellular organization was suggestive of increased synthetic and secretory activity. The decrease in the number of epithelial cells, with the prevalence of phenotypically immature subsets, was evident within the residual islands of thymic medullary tissue.

show abstract

Section: Introductionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Ultrastructure of different types of thymic epithelial cells in normal and cyclosporin-A-treated rats

Milićević¹,

Milićević²

1997

Anatomy and Embryology

View full text Add to dashboard Cite

show abstract

“…They have demonstrated by anti-keratin and MHC class I1 im- munolabeling that the epithelial network in the deep cortex and subcapsular area becomes coarser and denser in Wistar rats after CsA treatment. 253,254 Despite the considerable phenotypic similarity between subcapsular and medullary thymic EC, these cell populations apparently react differentially to CsA treatment. 254 The number of cortical EC was not decreased.254 In addition, cortical M(I were affected in CsA-treated Wistar rats.…”

Section: Alterations In the Cortexmentioning

confidence: 98%

“…253,254 Despite the considerable phenotypic similarity between subcapsular and medullary thymic EC, these cell populations apparently react differentially to CsA treatment. 254 The number of cortical EC was not decreased.254 In addition, cortical M(I were affected in CsA-treated Wistar rats. These cells became enlarged, and their succinic dehydrogenenase and chloroacetate esterase activities changed ~ubstantially.~~~ In contrast to the findings of Milicevic and co-workers, we and other investigators were unable to detect by immunohistochemistry any major CsA-induced changes in the subcapsular area of either the PVG and WAG/CPB rat thymus336 or the mouse thymus.97 In Lewis rats, a loss of MHC class I1 antigen in the subcapsular area has been observed after long-term administration of C S A .~~~…”

Section: Alterations In the Cortexmentioning

confidence: 98%

Differential Effects of 2,3,7,8-Tetrachlorodibenzo-P-Dioxin,bis(Tri-N-Butyltin)Oxide and Cyclosporine on Thymus Histophysiology

Ej¹,

Hj²,

H³

et al. 1997

Critical Reviews in Toxicology

View full text Add to dashboard Cite

Recent advances in the histophysiology of the normal thymus have revealed its complex architecture, showing distinct microenvironments at the light and electron microscopic level. The epithelium comprising the major component of the thymic stroma is not only involved in the positive selection of thymocytes, but also in their negative selection. Dendritic cells, however, are more efficient than epithelial cells in mediating negative selection. Thymocytes are dependent on the epithelium for normal development. Conversely, epithelial cells need the presence of thymocytes to maintain their integrity. The thymus rapidly responds to immunotoxic injury. Both the thymocytes and the nonlymphoid compartment of the organ can be targets of exposure. Disturbance of positive and negative thymocyte selection may have a major impact on the immunological function of the thymus. Suppression of peripheral T-cell-dependent immunity as a consequence of thymus toxicity is primarily seen after perinatal exposure when the thymus is most active. Autoimmunity may be another manifestation of chemically mediated thymus toxicity. Although the regenerative capacity of thymus structure is remarkable, it remains to be clarified whether this also applies to thymus function. In-depth mechanistic studies on chemical-induced dysfunction of the thymus have been conducted with the environmental contaminants 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and bis(tri-n-butyltin)oxide (TBTO) as well as the pharmaceutical immunosuppressant cyclosporine (CsA). Each of these compounds exerts a differential effect on the morphology of the thymus, depending on the cellular targets for toxicity. TCDD and TBTO exposure results in cortical lymphodepletion, albeit by different mechanisms. An important feature of TCDD-mediated thymus toxicity is the disruption of epithelial cells in the cortex. TBTO primarily induces cortical thymocyte cell death. In contrast CsA administration results in major alterations in the medulla, the cortex remaining largely intact. Medullary epithelial cells and dendritic cells are particularly sensitive to CsA. The differential effects of these three immunotoxicants suggest unique susceptibilities of the various cell types and regions that make up the thymus.

show abstract

Alterations of dendritic cells in the rat thymus without epithelial cell loss during cyclosporine treatment and recovery

Waal¹,

Rademakers²,

Schuurman³

et al. 1996

Toxicology

View full text Add to dashboard Cite

Differential effect of cyclosporin application on epithelial cells of the rat thymus. Immunohistochemical study

Cited by 10 publications

References 9 publications

Ultrastructure of different types of thymic epithelial cells in normal and cyclosporin-A-treated rats

Ultrastructure of different types of thymic epithelial cells in normal and cyclosporin-A-treated rats

Differential Effects of 2,3,7,8-Tetrachlorodibenzo-P-Dioxin,bis(Tri-N-Butyltin)Oxide and Cyclosporine on Thymus Histophysiology

Alterations of dendritic cells in the rat thymus without epithelial cell loss during cyclosporine treatment and recovery

Contact Info

Product

Resources

About