Control of Leukocyte Trafficking by Stress-Associated Hormones

Abstract

Leukocyte migration is a crucial process in both homeostatic and inflammatory conditions. The spatiotemporal distribution of immune cells is balanced between processes of cellular mobilization into the bloodstream, their adhesion to vascular beds and trafficking into tissues. Systemic regulation of leukocyte mobility is achieved by different signals including neuronal and hormonal cues, of which the catecholamines and glucocorticoids have been most extensively studied. These hormones are often associated with a stress response, however they regulate immune cell trafficking also in steady state, with effects dependent upon cell type, location, time-of-day, concentration, and duration of signal. Systemic administration of catecholamines, such as the sympathetic neurotransmitters adrenaline and noradrenaline, increases neutrophil numbers in the bloodstream but has different effects on other leukocyte populations. In contrast, local, endogenous sympathetic tone has been shown to be crucial for dynamic daily changes in adhesion molecule expression in the bone marrow and skeletal muscle, acting as a key signal to the endothelium and stromal cells to regulate immune cell trafficking. Conversely, glucocorticoids are often reported as anti-inflammatory, although recent data shows a more complex role, particularly under steady-state conditions. Endogenous changes in circulating glucocorticoid concentration induce redistribution of cells and potentiate inflammatory responses, and in many paradigms glucocorticoid action is strongly influenced by time of day. In this review, we discuss the current knowledge of catecholamine and glucocorticoid regulation of leukocyte migration under homeostatic and stimulated conditions.

Regulatory T cells confer a circadian signature on inflammatory arthritis

“…This is in part due to cell-autonomous circadian clocks within immune cells, driving daily variation in cell function, including trafficking [2][3][4] , cytokine release 5,6 and phagocytosis 7 . Additionally, rhythmic circadian outputs, such as hormones, can drive daily changes in immune cell function 8,9 .…”

Does exposure to parasites modify relationships between diurnal cortisol and leukocytes among Honduran women?

“…Granulocytes are comprised of neutrophils, basophils, eosinophils, and mast cells. The trafficking of granulocytes is complex, as some granulocytic cells are regulated by the action of glucocorticoids on the expression of circadian regulator genes (e.g., mast cells and basophils) (Pick, He, Chen, & Scheiermann, 2019), while others are regulated primarily through altering their lifespan or their adhesion to vascular walls, without directly influencing their expression (e.g., neutrophils) (Ince et al, 2019). Furthermore, IgE promotes mast cell and basophil survival and proliferation, and mast cells control actual trafficking of neutrophils (Burton & Oettgen, 2012).…”

“…Furthermore, if low IgE is indicative of having proportionally higher neutrophilic granulocytes, this may also explain why cortisol is positively associated with granulocytes in these individuals cross‐sectionally. Since glucocorticoids are linked to increased levels of neutrophils in the periphery through non‐circadian pathways (e.g., suspension of apoptosis and increased demarginalization), it is logical that this relationship would be stronger among individuals whose granulocytes are comprised of a higher proportion of neutrophils (Ince et al, 2019; Schleimer, Freeland, Peters, Brown, & Derse, 1989).…”

“…A number of cells and signaling molecules of the immune system follow antiphasic diurnal rhythms to—and are largely controlled by— circulating glucocorticoids (Chrousos, 1999; Cermakian et al, 2013; for a comprehensive review: Labrecque & Cermakian, 2015). For example, diurnal fluctuation in glucocorticoids, in conjunction with non HPA‐derived hormones (e.g., melatonin, 17β‐oestradiol), modulate the expression of various chemokines, β‐adrenergic receptors and chemokine receptors, which mediate circadian homing patterns in leukocytes (Butcher & Picker, 1996; Ince, Weber, & Scheiermann, 2019; Straub, Cutolo, Buttgereit, & Pongratz, 2010). In humans, peripheral lymphocytes are at their lowest early in the day, in parallel with the morning cortisol spike, and peak during evening hours when cortisol levels are falling (Ackermann et al, 2012; Haus & Smolensky, 1999).…”

Relative white blood cell counts, heterophil-to-lymphocyte ratio, and discovery of blood parasites in wild dugong (Dugong dugon) at Lingayan Island, Toli-toli, Indonesia

“…However, cortisol also increases heterophil migration from the bone marrow to the bloodstream and prevents heterophil transfer from blood to other compartments. Therefore, the stress response determined from peripheral blood vessels includes neutrophilia and lymphopenia [ 15 ]. This results in an increased H/L ratio compared to that in normal conditions.…”