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

Departments of ¹Internal Medicine, ²Immunology, and ⁴Pathology, Josephine Nefkens Institute, Erasmus MC, 3015 GD Rotterdam, The Netherlands; and ³Radiology Department, Washington University School of Medicine, St. Louis, Missouri 63110

Submitted 3 February 2003 ; accepted in final form 6 April 2003

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_1–5) 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 time-dependent regulation of sst_1–5, SS, and cortistatin (CST), a novel SS-like peptide, in human monocytes (MO), monocyte-derived macrophages (MP), and dendritic cells (DC) in the basal and lipopolysaccharide (LPS)-activated state. MO, MP, and DC selectively expressed sst₂ mRNA. SS mRNA was not detectable, whereas all samples expressed CST mRNA. Expression levels of sst₂ and CST mRNA showed marked differences and were in the rank order of MP>>DC>>>MO. 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, time-dependent, significantly increasing sst₂ 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 sst₂, in human monocyte-derived cells, suggesting a role for a CST-sst₂ system rather than a SS-sst₂ system in these immune cell types.

cellular differentiation; cellular activation; neuropeptides; messenger ribonucleic acid

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