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Published online November 30, 2009
The Journal of Immunology, 2010, 184, 503 -511
Copyright © 2010 by The American Association of Immunologists, Inc.
doi:10.4049/jimmunol.0902189

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Selective Mobilization of Cytotoxic Leukocytes by Epinephrine

Stoyan Dimitrov,*1 Tanja Lange,*{dagger} and Jan Born*

*Department of Neuroendocrinology and {dagger}Department of Internal Medicine, University of Lübeck, Lübeck, Germany

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, CCR7CD45RA+CD8+ effector T cells, CD4CD8 {gamma}/{delta} 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 CD62LCD11abrightCX3CRbright 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.

Address correspondence and reprint requests to Dr. Tanja Lange, Department of Neuroendocrinology, University of Lübeck, Ratzeburger Allee 160, Haus 23a, 23538 Lübeck, Germany. E-mail address: lange{at}kfg.uni-luebeck.de

1 Current address: Cousins Center for Psychoneuroimmunology, University of California, Los Angeles, CA.

The study was funded by a grant from the Deutsche Forschungsgemeinschaft (SFB 654: Plasticity and Sleep).

Abbreviations used in this article:

CM, central memory; EFF, effector T cells; EM, effector memory; MFI, mean fluorescence intensity; SNS, sympathetic nervous system.


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