title: Catecholamines are synthesized by mouse lymphocytes and regulate function of these cells by induction of apoptosis.
abstract: The immune and the nervous systems are anatomically closely related and interact with each other by molecules common to both systems, such as cytokines and neurotransmitters. The purpose of this study was to investigate the participation of catecholamines in the neuroimmunological network. The ability of immune cells to produce catecholamines was examined by a highly sensitive capillary electrophoresis assay, which permits detection of easily oxidized catecholamines in the zeptomole (10(-21)) range. In addition, the effects of catecholamines on in vitro proliferation, differentiation and apoptosis of lymphocytes were assessed. Mouse spleen cells and macrophages contained on average 7 x 10(-17) and 2 x 10(-17) mole dopamine per cell, respectively. In the former cell population also norepinephrine was found. Several mouse B- and T-cell hybridomas were also shown to contain endogenously produced dopamine in levels ranging from 7 x 10(-20) to 2 x 10(-18) mole dopamine per cell. In addition, one of the T-cell hybridomas proved to synthesize norepinephrine. The dopamine production of lymphocytes was blocked by the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine, whereas incubation with the precursor L-DOPA increased the dopamine content. Incubation with L-DOPA, dopamine and norepinephrine dose-dependently suppressed mitogen induced proliferation and differentiation of mouse lymphocytes. Even short-time pretreatment of lymphocytes with L-DOPA and dopamine strongly suppressed lymphocyte proliferation and cytokine production. Incubation of lymphoid cells with L-DOPA, dopamine and norepinephrine dose-dependently induced apoptosis which, at least partly, explains the suppressive effects of catecholamines on lymphocyte function. Our results demonstrate that catecholamines: (i) are actively produced by lymphocytes and (ii) have the capacity to act as auto- and/or paracrine regulators of lymphocyte activity through induction of apoptosis.
authors.affiliation: Department of Clinical Immunology, University of Göteborg, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Josefsson
authors.forename: J
authors.initials: J
authors.lastname: Bergquist
authors.forename: R
authors.initials: R
authors.lastname: Ekman
authors.forename: A
authors.initials: A
authors.lastname: Tarkowski
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002395:Catecholamines / Q000032:analysis / Q000096:biosynthesis* / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D004298:Dopamine / Q000032:analysis / Q000096:biosynthesis / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019075:Electrophoresis, Capillary; D005260:Female; D007980:Levodopa / Q000494:pharmacology; D008214:Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008811:Mice, Inbred DBA; D009638:Norepinephrine / Q000032:analysis / Q000096:biosynthesis / Q000494:pharmacology
chemical_list: D002395:Catecholamines; D016207:Cytokines; D007980:Levodopa; D004298:Dopamine; D009638:Norepinephrine