Differential expression of somatostatin receptor subtypes in human peripheral blood mononuclear cell subsets

Abstract

Background: Somatostatin (SS)-binding sites have been demonstrated in human lymphoid tissues and peripheral blood cells. However, not much is known with respect to the SS receptor subtype (sst) expression pattern and the expression of SS itself in the immune system. Objective: The aim of this study was to evaluate the mRNA expression of the five known sst (sst 1 -5 ) in peripheral blood mononuclear cell (sub)populations. Moreover, the expression of the mRNAs encoding SS and the SS-like peptide cortistatin (CST) in immune cell subsets was studied. Methods: RT-PCR and quantitative PCR were performed to evaluate sst, SS and CST mRNA expression in cells in the basal or activated state. Fluorescence-activated cell sorter (FACS) analysis using fluorescent SS was performed to visualize sst protein on cell membranes. Results: B-and T-lymphocytes selectively expressed sst 3 mRNA. sst 3 expression in B-lymphocytes was significantly lower compared with T-lymphocytes. Unstimulated, freshly isolated monocytes did not express any sst mRNA. Upon activation, monocytes selectively expressed sst 2 mRNA, whereas T-lymphocyte activation upregulated sst 3 expression. sst 2 mRNA expression on monocytes was confirmed by FACS analysis. B-and T-lymphocytes did not express SS mRNA, while both cell types expressed CST mRNA. CST mRNA expression was downregulated following T-lymphocyte activation. Conclusion: We demonstrate for the first time unequivocally that human peripheral blood B-and T-lymphocytes selectively express sst 3 , whereas monocytes do not express sst. However, upon activation, monocytes are induced to express sst 2A . No expression of SS mRNA was detected in any cell type, whereas all cell types expressed CST mRNA. The differential expression of sst and CST mRNA in lymphocytes and monocytes suggests a functional significance for the CST -sst interaction in immune cells, but further studies should be performed to evaluate the significance of sst and CST in these cells.

The role of cortistatin in the human immune system

“…We demonstrated unequivocally that human peripheral blood B-and T-lymphocytes selectively express sst 3 , whereas monocytes do not express sst. However, upon activation, monocytes are induced to express sst 2 (table 1) (Lichtenauer- Kaligis et al, 2004).…”

“…In the murine immune system predominantly sst 2 and sst 4 are expressed, while in human immune cells predominantly sst 2 and sst 3 are expressed in distinct cell subsets (Lichtenauer-Kaligis et al, 2004;ten Bokum et al, 2002).…”

“…Expression of SRIF and cortistatin (CST) and their receptors in the human immune system and malignancies of the immune system (Dalm et al, 2003b;Dalm et al, 2004a;Dalm et al, 2003c;Dalm et al, 2004b;Ferone et al, 2004;Ferone et al, 2002;Lichtenauer-Kaligis et al, 2004;Oomen et al, 2000;ten Bokum et al, 2000;ten Bokum et al, 1999a;ten Bokum et al, 1999c;van Hagen et al, 1999 A c c e p t e d M a n u s c r i p t M a n u s c r i p t M a n u s c r i p t M a n u s c r i p t…”

Expression, pharmacology, and functional role of somatostatin receptor subtypes 1 and 2 in human macrophages

“…In rodent cells of the monocyte lineage, the inhibitory role of SRIF-14 has been studied extensively [7][8][9][10][11][12][13][14]. However, in human monocytes, the role of SRIF-14 is less well-understood, and reported results have been controversial [5,15]. Human monocytes derived from PBMC do not express mRNA for SRIF-14 [16 -18], and they do express the mRNA for cortistatin [16,17], a SRIF-14-like peptide, which may serve as an alternative ligand for SRIF receptors in the immune system [19,20].…”

“…The presence of SRIF receptors in monocytes has been suggested from binding studies [4,5]. In addition, sst 2 mRNA has been observed in PBMC-derived monocytes [17]; however, this expression was undetectable under basal conditions and required cell activation to upregulate the mRNA to a level that could be detected [15]. Circulating monocytes are versatile precursor cells with the ability to differentiate into various forms of specialized macrophages [21,22], a process that is influenced profoundly by the cytokine milieu.…”