Mouse Adrenal Macrophages Are Associated with Pre- and Postsynaptic Neuronal Elements and Respond to Multiple...

The adrenal medulla is packed with chromaffin cells, modified postganglionic sympathetic neurons that secrete the catecholamines, epinephrine and norepinephrine, during the fight-or-flight response. Sometimes overlooked is a population of immune cells that also resides within the gland but whose distribution and function are not clear. Here I examine the location of CD45+ hematopoietic cells in the mouse adrenal medulla and show the majority are F4/80+/Lyz2+ macrophages. These cells are present from early postnatal development and widely distributed. Anatomically they are associated with chromaffin cells, found aligned alongside synapsin-IR neuronal varicosities and juxtaposed to CD31-IR blood vessels. Using Lyz2cre-GCaMP6f mice to quantify calcium signaling in macrophages revealed these cells respond directly and indirectly to a wide variety of neuromodulators, including pre- and postganglionic transmitters and systemic hormones. Purinergic agonists, histamine, acetylcholine, and bradykinin rapidly and reversibly increased intracellular calcium. These results are consistent with a substantial resident population of innate immune cells in the adrenal medulla. Their close association with chromaffin cells and the preganglionic input suggests they may regulate sympatho-adrenal activity and thus the strength of the fight-or-flight response.