Selective Mobilization of Cytotoxic Leukocytes by Epinephrine

Epinephrine selectively mobilizes cytotoxic effector cells. Mean (± SEM) numbers of (A, E, naive [CCR7⁺CD45RA⁺]), (B, F, CM [CCR7⁺CD45RA^–]), (C, G, EM [CCR7^–CD45RA^–]), and (D, H, EFF [CCR7^–CD45RA⁺]) CD4⁺ (left) and CD8⁺ (right) T cells, of (I) γ/δ T cells (CD3⁺CD4⁻CD8⁻), (J) NKT-like cells (CD3⁺CD56⁺), (K) immunomodulatory NK cells (CD56⁺ NK, CD16⁻CD56^bright), (L) cytotoxic NK cells (CD16⁺ NK, CD16⁺CD56^dim), (M) conventional monocytes (CD14⁺ Mo, CD14⁺CD16⁻), and (N) proinflammatory monocytes (CD16⁺ Mo, CD14^dimCD16⁺) after a 30-min i.v. infusion (horizontal gray bar) of placebo (sodium chloride, open circles) and epinephrine (filled circles); n = 8, *p < 0.05, **p < 0.01 for pairwise comparison between epinephrine and placebo conditions.

Adhesion molecule and chemokine receptor expression on leukocyte subsets. A, Representative dotplots of naive (CCR7⁺CD45RA⁺CD4⁺ [a]), CM (CCR7⁺CD45RA⁻CD4⁺ [b]), EM (CCR7⁻CD45RA⁻CD4⁺ [c]), and effector (CCR7⁻CD45RA⁺CD4⁺ [d]) Th cells; naive (CCR7⁺CD45RA⁺CD8⁺ [e]), CM (CCR7⁺CD45RA⁻CD8⁺ [f]), EM (CCR7⁻CD45RA⁻CD8⁺ [g]), and effector (CCR7⁻CD45RA⁺CD8⁺ [h]) cytotoxic T cells; γ/δ T cells (CD3⁺CD4⁻CD8⁻ [i]), NKT-like cells (CD3⁺CD56⁺ [j]), immunomodulatory NK cells (CD16⁻CD56^bright [k]), cytotoxic NK cells (CD16⁺CD56^dim [l]), conventional monocytes (CD14⁺CD16⁻ [m]), and proinflammatory monocytes (CD14^dimCD16⁺ [n]). Lowercase letters refer to respective cell subset; subpopulations mobilized by epinephrine in vivo are in bold. B, Surface expression of chemokine receptors (CCR5, CXCR1, CXCR3, and CX3CR1), L-selectin (CD62L), and three integrins (CD11a, CD11b, and CD49d). Mean (± SEM) percentages or MFI of cells for respective subset in six to eight healthy donors. Black bars indicate subpopulations mobilized by epinephrine in vivo; y-axis for CX3CR1 MFI is log-transformed. C, Correlations between CD11a and CX3CR1 expression and increases after epinephrine in vivo across different leukocyte subsets. Filled circles indicate subpopulations mobilized by epinephrine in vivo. For calculating correlation coefficients, cytotoxic NK cells (l) were excluded because of their clearly exaggerated response (3-fold increase) to epinephrine in vivo. **p < 0.01, ***p < 0.001.

Representative examples of cell surface expression of CX3CR1 on leukocyte subpopulations. The lowercase letters indicating subpopulations are the same as in Fig. 3.

Epinephrine selectively mobilizes CX3CR1⁺ T cells. Mean (± SEM) numbers of (A) CCR5⁺, (B) CXCR1⁺, (C) CXCR3⁺, and (D) CX3CR1⁺ T cells after a 30-min i.v. infusion (horizontal gray bar) of placebo (sodium chloride, open circles) and epinephrine (filled circles); n = 8. **p < 0.01 for pairwise comparison between epinephrine and placebo conditions.