Expression of somatostatin, cortistatin, and somatostatin receptors in human monocytes, macrophages, and dendritic cells

Abstract

Increasing evidence suggests that neuropeptides play a role in the regulatory mechanisms between the neuroendocrine and immune systems. A differential expression of the five known somatostatin (SS) receptors (sst [1][2][3][4][5] has been demonstrated in human immune cells and tissues. However, little is known concerning regulation and expression of sst 1-5 and the peptide SS. Therefore, we investigated the expression and the timedependent regulation of sst 1-5, SS, and cortistatin (CST), a novel SS-like peptide, in human monocytes (MO), monocytederived macrophages (MP), and dendritic cells (DC) in the basal and lipopolysaccharide (LPS)-activated state. MO, MP, and DC selectively expressed sst 2 mRNA. SS mRNA was not detectable, whereas all samples expressed CST mRNA. Expression levels of sst 2 and CST mRNA showed marked differences and were in the rank order of MPϾϾDCϾϾϾMO. LPS stimulation did not induce expression of SS or sst 1,3,4,5. However, sst2 mRNA expression was upregulated significantly by stimulation with LPS. CST mRNA was upregulated as well. During differentiation of MO in MP or DC, timedependent, significantly increasing sst 2 and CST mRNA levels were found. By confocal microscopy, the presence of sst2 receptors was demonstrated on MP, but not on DC. This study demonstrates for the first time a selective and inducible expression of the recently discovered CST, as well as sst 2, in human monocyte-derived cells, suggesting a role for a CST-sst 2 system rather than a SS-sst2 system in these immune cell types.

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

“…As discussed previously for monocytes, human macrophages differentiated from PBMC-derived monocytes have been shown recently to express cortistatin mRNA but not SRIF-14 mRNA [16,17]. In addition, they seem to express sst 2 mRNA and the related protein [17], although the functional significance of this expression pattern is still unknown.…”

“…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, they seem to express sst 2 mRNA and the related protein [17], although the functional significance of this expression pattern is still unknown. We therefore investigated in human macrophages differentiated from PBMC-derived monocytes the mRNA expression of SRIF receptors, the expression level of distinct SRIF receptor proteins and their trafficking in the presence of SRIF analogs, and the pharmacology and functional role of distinct SRIF receptors.…”

The role of cortistatin in the human immune system

“…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…”

Imaging Cardiovascular Calcification

“…In atherosclerotic inflammation, the surface of activated macrophages overexpresses the G‐protein‐coupled receptor somatostatin receptor subtype‐2 123. Preclinical124 and retrospective125, 126 studies suggest that gallium‐68‐labeled [1,4,7,10‐tetraazacy‐clododecane‐ N , N ′, N ″, N ‴‐tetraacetic acid]‐ d ‐Phe1, Tyr3‐octreotate (DOTATATE), a somatostatin receptor subtype‐2‐binding PET tracer, may be superior to 18 F‐FDG for imaging atherosclerotic inflammation.…”