Expression of functional insulin-like growth factor-1 receptor on lymphoid cell subsets of rats.
It has become evident that insulin-like growth factor-1 (IGF-1) acts as a growth factor for immune cells, yet the precise regulatory role of IGF-1 in the immune system is unknown. The aim of this study was to examine the distribution of IGF-1 receptors on rat lymphoid cells. A flow cytometric method was used, with a biotinylated and functionally active IGF-1 analogue, namely des(1-3)IGF-1, which binds well to IGF-1 receptor but poorly to IGF binding proteins, followed by phycoerythrin-conjugated streptavidin (PE-SA) staining. Our results showed that IGF-1 receptors were readily detectable on a wide variety of the immune cells, including T cells, B cells and monocytes, but the binding capacity for IGF-1 was monocytes > B cells > T cells, as determined by titration experiments. Furthermore, the level of expression on resting CD4+ T lymphocytes was greater than on CD8+ cells, and the concentration of biotin-des(1-3)IGF-1 required to demonstrate the binding to IGF-1 receptor on CD8+ cells (68 nmol/l) was 200-fold higher than for CD4+ cells (0.34 nmol/l), indicating that most of the IGF-1 receptor on CD8+ cells represented lower affinity sites. The level of IGF-1 receptor expression was increased several-fold after concanavalin A stimulation on both CD4+ and CD8+ T-cell subsets. Kinetic analysis of the expression of IGF-1 receptor and its association with interleukin-2 receptors (IL-2R) following activation showed a similar pattern, with no significant differences in the ratio of IGF-1 receptor: IL-2R per cell during the 3 days of cell culture. Our studies suggest that biological activities of IGF-1 include direct stimulation of immune cells, and that expression of IGF-1 receptor may have a role in regulation of T-cell function.
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Cooperative Research Centre for Tissue Growth and Repair, Child Health Research Institute, North Adelaide, Australia.
Mardell
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Xian
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Zola
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Read
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D000818:Animals; D001667:Binding, Competitive; D003208:Concanavalin A / Q000276:immunology; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000378:metabolism*; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D013154:Spleen / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation
D010446:Peptide Fragments; D003208:Concanavalin A; C058957:insulin-like growth factor 1, des-(1-3)-; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1