Expression of substance P and its neurokinin-1 receptor on thymocytes: functional relevance in the regulation of thymocyte apoptosis and proliferation.

Giorgio Santoni, Consuelo Amantini, Roberta Lucciarini, Pierluigi Pompei, Marina Perfumi, Massimo Nabissi, Stefania Morrone, Mario Piccoli

Department of Pharmacological Sciences and Experimental Medicine, University of Camerino, Camerino, Italy. giorgio.santoni@unicam.it

Neuroimmunomodulation 2002-2003

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Herein, we provide evidence of the expression and function of substance P (SP) and neurokinin-1 receptor (NK-1R) in the rat thymus. In situ hybridization evidenced NK-1R mRNA mainly in the thymic medulla, and Northern blot analysis of mRNA from FACS-sorted thymocytes identified NK-1R on CD4+, CD8+ and double-positive subpopulations. With flow cytometry, it could be seen that NK-1R was expressed on the majority of CD5+ thymocytes, and it was identified by Western blot analysis as two bands migrating at 44 and 54 kD. SP administration rescues thymocytes from spontaneous and NK-1R antagonist (SR140333)-induced apoptosis and stimulates concanavalin A (ConA)-induced thymocyte proliferation, CD25 expression and IL-2 production, whereas SR140333 exerts inhibitory effects on these functions. We also demonstrated the expression of mRNA for the SP precursor preprotachykinin-A in the thymic medulla and purified CD5+ thymocytes. SP protein was detected on 40% of CD5+ thymocytes and identified as a band of 1.3 kD by Western blot analysis. Finally, thymocytes spontaneously released SP, which was increased upon ConA or CD3 stimulation. Copyright 2003 S. Karger AG, Basel

Citation

Giorgio Santoni, Consuelo Amantini, Roberta Lucciarini, Pierluigi Pompei, Marina Perfumi, Massimo Nabissi, Stefania Morrone, Mario Piccoli. Expression of substance P and its neurokinin-1 receptor on thymocytes: functional relevance in the regulation of thymocyte apoptosis and proliferation. Neuroimmunomodulation. 2002-2003;10(4):232-46