Figure 2.

Regulation of leukocyte migration and trafficking by the SNS. (A) Homeostatic regulation of leukocyte trafficking is influenced by diurnal oscillations in SNS activity and increased noradrenaline release during the active phase (day in humans, night in mice). Endothelial cells and leukocytes increase expression of adhesion molecules and chemokines or chemokine receptors and promote leukocyte entry into tissues (1). In LNs, the circadian increase in noradrenaline stimulates reduced lymphocyte egress via β₂-adrenoceptors (β₂AR) and the chemokine receptors CXCR4 and CCR7 (2). (B) Increased sympathetic activity in response to stress, exercise, or pharmacological adrenergic agonists induces a rapid increase in leukocyte numbers in the blood within minutes (1), followed by a decrease in circulating lymphocyte numbers (2). (C) Increased sympathetic activity induces blood vessel constriction, reduced blood flow and tissue oxygenation. Leukocytes respond to hypoxia through calcium signaling that impairs cell motility, impacting tissue egress and cellular immunity (3).