Recently it has become clear that many of the intercellular communication pathways found in the central nervous system have parallels in the immune system. In this thesis, we present data which suggests that serotonin and its cognate receptors play an integral role in the process of lymphocytic activation and proliferation. We will show that serotonin is manipulated by peripheral blood mononuclear cells (PBMCs) in an in vitro experimental system. We will identify RNA and protein encoding two specific serotonergic receptors in PBMCs. Indirect immunofluorescence will show that serotonin and its receptors are localized in discrete, functional locations of monocytes and T cells. Receptor-specific pharmacological agents will be used to show that inhibiting these specific receptors inhibits T cell activation and proliferation. Finally, flow cytometry will be used to show that inhibition of the 5-HT1B and 5-HT2C receptors differentially inhibit T cell activation at unique points in the cascade. Selective withdrawal of the 5-HT2C receptor signal will be shown to inhibit the activation of T cells at a point prior to the activation of protein kinase C, while selective withdrawal of the 5-HT1B receptors signal will be shown to inhibit T cell activation downstream of this kinase. This is the first study to demonstrate differential inhibition of T cell activation via the inhibition of individual T cell serotonin receptors.
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Details
Title
Signaling through serotonin 1B and 2C receptors on lymphocytes is essential to T cell activation and proliferation
Creators
Ross H. Albert
Contributors
Bradford Aldrich Jameson (Advisor)
Awarding Institution
Drexel University
Degree Awarded
Doctor of Philosophy (Ph.D.)
Publisher
Drexel University; Philadelphia, Pennsylvania
Number of pages
9 unnumbered pages, 95 pages
Resource Type
Dissertation
Language
English
Academic Unit
Microbiology and Immunology; College of Medicine; Drexel University
Other Identifier
991014970197604721
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