Selective mobilization of cytotoxic leukocytes by epinephrine.
It is well-known that acute stress, presumably as a first defense against pathogens, enhances PBMC counts by mobilizing these beta2-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(-) gamma/delta T cells, CD3(+)CD56(+) NKT-like cells, CD16(+)CD56(dim) cytotoxic NK cells, and CD14(dim)CD16(+) proinflammatory monocytes showed a rapid and transient increase after infusion of epinephrine at physiological concentrations. These cells were characterized by a CD62L(-)CD11a(bright)CX3CR(bright) 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.
Dimitrov
Stoyan
S
Department of Neuroendocrinology, University of Lübeck, Lübeck, Germany.
Lange
Tanja
T
Born
Jan
J
D000322:Adrenergic Agonists / Q000494:pharmacology*; D000328:Adult; D002448:Cell Adhesion / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects*; D008297:Male; D009000:Monocytes / Q000187:drug effects*; D016176:T-Lymphocyte Subsets / Q000187:drug effects*; D055815:Young Adult
D000322:Adrenergic Agonists; D004837:Epinephrine