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Published online before print December 5, 2006

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(Journal of Leukocyte Biology. 2007;81:845-855.)
© 2007 by Society for Leukocyte Biology

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

Chiara Armani^*, Elisabetta Catalani, Alberto Balbarini^*, Paola Bagnoli and Davide Cervia^,,1

^* Cardiac Thoracic and Vascular Department, University of Pisa, Pisa, Italy;
Department of Environmental Sciences, University of Tuscia, Viterbo, Italy; and
Department of Biology, Unit of General Physiology, University of Pisa, Pisa, Italy

¹ Correspondence: Department of Environmental Sciences, University of Tuscia, Largo dell’Università snc, Blocco D, 01100 Viterbo, Italy. E-mail: d.cervia{at}unitus.it

Somatostatin (SRIF)-14 is recognized as an important mediator between the nervous and the immune system, although the functional role of its receptors (sst₁–sst₅) is poorly understood in humans. In our study, we demonstrate that human macrophages, differentiated from PBMC-derived monocytes, express sst₁ and sst₂ mRNAs. sst₁ and sst₂ are mostly localized at the cell surface and display active binding sites. In particular, sst₁/sst₂ activation results in a weak internalization of sst₁, and the sst₂ internalization appears more efficient. At the functional level, the activation of SRIF receptors by the multiligand analogs SOM230 and KE108, but not by SRIF-14 or cortistatin-14, reduces macrophage viability. Their effects are mimicked by the selective activation of sst₁ and sst₂ using CH-275 and SMS 201-995/L-779,976, respectively. Further, sst₁- and sst₂-mediated effects are reversed by the sst₁ antagonist SRA-880 or the sst₂ antagonist CYN 154806, respectively. CH-275, SMS 201-995, and L-779,976, but not SRIF-14, decrease mRNA expression and secretion of the MCP-1. In addition, SRIF-14, CH-275, SMS 201-995, and L-779,976 decrease IL-8 secretion, and they do not affect IL-8 mRNA expression. In contrast, SRIF-14 and sst₁/sst₂ agonists do not affect the secretion of matrix metalloproteinase-9. Collectively, our results suggest that the SRIF system, through sst₁ and sst₂, exerts mainly an immunosuppressive effect in human macrophages and may, therefore, represent a therapeutic window that can be exploited for the development of new strategies in pharmacological therapy of inflammation.

Key Words: neuropeptides • monocytes • trafficking • cell viability • chemokines • metalloproteinases

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