Selective Mobilization of Cytotoxic Leukocytes by Epinephrine

Abstract

It is well-known that acute stress, presumably as a first defense against pathogens, enhances PBMC counts by mobilizing these β2-adrenoceptor positive cells from the marginal pool. Yet, only select leukocyte subsets participate in this phenomenon of adrenergic leukocytosis and underlying mechanisms are obscure. In this study, we analyzed in human blood adhesion molecule and chemokine receptor profiles in 14 leukocyte subsets, and responsiveness of subsets to epinephrine in vivo and in vitro. Five subsets, namely, CCR7−CD45RA+CD8+ effector T cells, CD4−CD8− γ/δ T cells, CD3+CD56+ NKT-like cells, CD16+CD56dim cytotoxic NK cells, and CD14dimCD16+ proinflammatory monocytes showed a rapid and transient increase after infusion of epinephrine at physiological concentrations. These cells were characterized by a CD62L−CD11abrightCX3CRbright phenotype, whereby expression of both CD11a and CX3CR1 was strongly correlated with adrenergic leukocytosis in vivo (r = 0.86 and 0.78, p < 0.005). The same subsets showed highest adherence to activated endothelium in vitro, which (except for proinflammatory monocytes) was reversed by epinephrine. We conclude that these five cytotoxic effector leukocyte subsets comprise the marginal pool by a CD11a/CX3CR1-mediated attachment to the endothelium. Epinephrine rapidly attenuates this attachment to allow demargination and release of the cells into the circulation that, because of their cytotoxic effector function, provide immediate protection from invading pathogens.

Effect of acute and regular exercise on growth hormone secretagogue receptor-1a expression in human lymphocytes, T cell subpopulation and monocytes

“…The recruitment of lymphocytes and monocytes into the circulation is largely related to adrenergic-mediated demargination and extravasation of sequestered cells (Shephard, 2003;Kruger et al 2008), with cell subpopulations that are selectively deployed in response to an exercise stimulus also being those with the greatest expression of β2-adrenoreceptors or with greatest affinity for epinephrine (Shephard, 2003;Dimitrov et al, 2010). These recruited cells appear also to be those with potent effector/cytotoxic functions whereas those that preferentially transmigrate into the tissues have tissue migratory phenotypes (Simpson et al, 2008;Turner et al, 2010).…”

Human Spinal Cord Injury Causes Specific Increases in Surface Expression of Beta Integrins on Leukocytes

“…The hallmark of the inflammatory reaction to SCI is the large numbers of leukocytes that invade the injured spinal cord (Blight, 1992;Fleming et al, 2006;Saville et al, 2004), and bystander organs such as the lungs and kidneys (Gris et al, 2008). In response to stress or injury, leukocytes are released into the blood from marginal pools and the bone marrow (Dimitrov et al, 2010;Steppich et al, 2000), increasing the number of cells available to participate in inflammation-associated secondary injury in the central nervous system (CNS) lesion, and elsewhere in the body. Upon activation in the circulation, leukocytes can upregulate expression of their oxidative enzymes (Bao et al, 2009).…”

Effects of General and Local Anaesthesia on Innate and Cell-Mediated Immunity in Dogs

“…The actual mechanism of this effect is demargination of leucocytes and moving of functionally active but, not drowsy cells in the circulation. The trigger process for this effect is binding of released catecholamines to beta-2-adrenergic receptors on the surface of leucocytes and modifying the adhesion molecules (Dimitrov et al, 2010).…”