Catecholamines in Macrophages
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 A Collaborative Project: In 2002, Dr. Jennifer Stewart and her students
at VCU began collaborating with Dr.
Krista Fischer-Stenger and
students in the Department of Biology at the University
of Richmond to investigate the synthesis, release, and
actions of catecholamines in macrophages. Why Macrophages? These cells play major roles in both innate and acquired immunity. Macrophages engulf bacteria and other particles, process and present antigens to T-lymphocytes, and secrete molecules with both immunoregulatory and cytolytic activities. Who Sponsors this Research? This collaborative project is funded by the Molecular and Cellular Biology Program of the National Science Foundation. Students’ Projects: Catecholamine Synthesis in Macrophages: Graduate students Scott Brown, Randy Myers, and Karen Brennan and University of Richmond undergraduate Julie Rumble helped to demonstrate that a macrophage cell line synthesizes both dopamine and norepinephrine but releases predominantly norepinephrine. Scott Brown also demonstrated that macrophage production of glutathione is important in protecting macrophages from the anti-proliferative effects of norepinephrine and dopamine. Graduate student Karen Brennan found that mouse peritoneal macrophages express tyrosine hydroxylase, the rate-limiting enzyme for synthesis of all catecholamines. Catecholamine Transport in Macrophages: Karen Brennan has evidence that peritoneal macrophages express transport molecules needed to store catecholamines in vesicles; these vesicular monoamine transporters (VMAT 1 and 2) are important for both storage and regulated release of catecholamines. Meghan Roden Rudd has focused on identifying the cell membrane transporters that permit macrophages to take up catecholamines and other monoamines from extracellular fluids. She found that peritoneal macrophages express the serotonin transporter (SERT), which takes up both serotonin and dopamine, and she demonstrated that SERT activity in macrophages is blocked by the specific SERT inhibitor fluoxetine. Meghan and Sienna Malubay are working to determine whether macrophages express other transporters that take up norepinephrine and epinephrine. Chris Waggener is using immunocytochemistry to localize catecholamine transporters. Actions of Macrophage Catecholamines: Because macrophages have catecholamine receptors, the catecholamines released by macrophages can modulate macrophage function. An important function of macrophages is production of cytokines such as interleukins. Using catecholamine receptor blockers, graduate student Kristie Engler has demonstrated that macrophage-derived catecholamines act on the b2-adrenergic receptor to inhibit macrophage production of interleukin-1 beta (IL-1b) and on the a2-adrenergic receptor to stimulate IL-1b production. Graduate students Shaunta Poe and George Georges are investigating other actions of macrophage-derived catecholamines. |