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Somatostatin receptor (SSTR) expression and function in normal and leukaemic T-cells. Evidence for selective effects
T Talme1, J Ivanoff, M Hägglund
1Department of Medicine, Section of Dermatology and Venereology, Karolinska Institutet at Huddinge University Hospital, Huddinge, Sweden.
Abstract:
We have examined normal T-cells and T-cell lines with respect to expression of various somatostatin receptor subtypes (SSTR1--5) using RT-PCR and PCR. To evaluate the function of these receptors we have further studied the effects of subtype specific signalling on T-cell adhesion using somatostatin analogs specific for various receptors as probes. Human T-lymphocytes showed SSTR expression related to activation and stage of differentiation. Normal T-cells (peripheral blood, T-cell clone) and T-leukaemia cell lines expressed SSTR2, SSTR3 and SSTR4. Normal T-cells expressed SSTR1 and SSTR5 while T-leukaemia lines did not. SSTR5 was selectively expressed in activated normal T-cells. T-lymphocytes produced no somatostatin themselves. Somatostatin and somatostatin analogs specific for SSTR2 and/or SSTR3 enhanced adhesion of T-cells to fibronectin (FN), and to a certain extent, also to collagen type IV (CIV) and laminin (LAM). T-lymphocytes express multiple SSTR and somatostatin may therefore regulate lymphocyte functions via distinct receptor subtypes as shown here for adhesion to extracellular matrix components (ECM) via SSTR2 and SSTR3. SSTR expression also distinguishes normal and leukaemic T-cells. Our findings suggest that SSTR subtypes may be useful targets for therapy during inflammatory diseases and malignancies affecting lymphocytes.
Insights
Normal T-cells express somatostatin receptors (SSTR1-5), with distinct patterns differentiating them from T-leukemia cells. Somatostatin enhances T-cell adhesion via SSTR2 and SSTR3, suggesting therapeutic potential.
Area of Science:
- Immunology
- Endocrinology
- Molecular Biology
Background:
- T-lymphocytes play crucial roles in immune responses.
- Somatostatin receptors (SSTRs) are implicated in various cellular functions.
- Understanding SSTR expression in T-cells can reveal insights into lymphocyte regulation.
Purpose of the Study:
- To investigate the expression of somatostatin receptor subtypes (SSTR1-5) in normal T-lymphocytes and T-leukemia cell lines.
- To explore the functional role of SSTRs in T-cell adhesion to extracellular matrix components.
- To determine if SSTR expression patterns can differentiate normal from leukaemic T-cells.
Main Methods:
- Reverse transcription-polymerase chain reaction (RT-PCR) and PCR were used to detect SSTR gene expression.
- Somatostatin analogs specific for various SSTR subtypes were employed to study functional effects.
- T-cell adhesion assays were performed using fibronectin, collagen type IV, and laminin as substrates.
Main Results:
- Normal T-cells expressed SSTR1, SSTR2, SSTR3, SSTR4, and SSTR5, with SSTR5 selectively found on activated cells.
- T-leukemia cell lines expressed SSTR2, SSTR3, and SSTR4, but lacked SSTR1 and SSTR5.
- Somatostatin and analogs targeting SSTR2/SSTR3 significantly enhanced T-cell adhesion to fibronectin, collagen type IV, and laminin.
Conclusions:
- T-lymphocytes express multiple SSTR subtypes, with distinct expression profiles in normal versus leukaemic cells.
- Somatostatin signaling through SSTR2 and SSTR3 can modulate T-cell adhesion to extracellular matrix components.
- SSTR subtypes represent potential therapeutic targets for inflammatory diseases and lymphoid malignancies.