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Constitutive Overexpression of the L-Selectin Gene in Fresh Leukemic Cells of Adult T-Cell Leukemia That Can Be Transactivated by Human T-Cell Lymphotropic Virus Type 1 Tax
- Source :
- Blood; October 1995, Vol. 86 Issue: 8 p3109-3117, 9p
- Publication Year :
- 1995
-
Abstract
- L-selectin is an adhesion molecule of the selectin family that mediates the initial step of leukocyte adhesion to vascular endothelium. Upon cellular activation, expression of the L-selectin gene is downregulated at both the protein and mRNA levels. To understand the mechanism of leukemic cell infiltration into organs, we studied the expression and regulation of L-selectin mRNA in fresh leukemic cells of adult T-cell leukemia (ATL) patients and investigated the response of the L-selectin promoter to human T-cell lymphotropic virus type 1 (HTLV-1) Tax, which is a viral transcriptional trans-activator. Flow cytometry showed that L-selectin was expressed on fresh ATL cells along with other activation antigens. Northern blot analysis showed that ATL cells over-expressed the L-selectin mRNA and that the level was aberrantly upregulated after PMA stimulation. Studies using in situ hybridization showed expression of the L-selectin mRNA in the infiltrating leukemic cells in the liver of two ATL patients. Intravenous injection of a rat T-cell line that overexpresses L-selectin showed increased organ infiltration. The induction of Tax expression in JPX9 cells resulted in about a twofold increase in the mRNA expression levels compared with the basal level. Chloramphenicol acetyrtrans-ferase (CAT) assay after transient cotransfection showed about a fivefold transactivation of the L-selectin promoter by Tax. The serum level of the shed form of L-selectin was significantly increased in ATL patients (mean ± SD, 4,215.4 ± 4,111 ng/mL) compared with those of asymptomatic carriers and healthy blood donors (mean ± SD, 1,148.0 ± 269.0 ng/ mL and 991.9 ± 224 ng/mL, respectively). These results indicated that ATL cells constitutively overexpress the L-selectin gene that can be transactivated by HTLV-1 Tax. The overexpression of L-selectin, as well as of inflammatory cytokines, by ATL cells may provide a basis for ATL cells to attach the vascular endothelium, leading to transmigration and organ infitration.
Details
- Language :
- English
- ISSN :
- 00064971 and 15280020
- Volume :
- 86
- Issue :
- 8
- Database :
- Supplemental Index
- Journal :
- Blood
- Publication Type :
- Periodical
- Accession number :
- ejs57041218
- Full Text :
- https://doi.org/10.1182/blood.V86.8.3109.3109