Cortisol-induced CXCR4 augmentation mobilizes T lymphocytes after acute physical stress.
The aim of this study was to elucidate the mechanism responsible for lymphopenia after exercise. Seven young healthy men volunteered for this study. Peripheral blood mononuclear cells (PBMC) were cultured with cortisol and analyzed for C-X-C motif chemokine receptor 4 (CXCR4) expression by flow cytometry. To determine the effects of exercise, subjects performed exhaustive cycling exercise. PBMC were cultured with plasma obtained before and after the cycling exercise. Alternatively, PBMC obtained before and after exercise were cultured without plasma or glucocorticoid to examine whether PBMC were primed in vivo for CXCR4 expression. We analyzed cortisol- or plasma-treated PBMC to determine their ability to migrate through membrane filters in response to stromal cell-derived factor 1alpha/CXCL12. Cortisol dose- and time-dependently augmented CXCR4 expression on T lymphocytes, with <6 h of treatment sufficient to augment CXCR4 on T lymphocytes. Postexercise plasma also augmented CXCR4 expression. Cortisol or postexercise plasma treatment markedly enhanced migration of T lymphocytes toward CXCL12. Augmentation of CXCR4 on T lymphocytes by cortisol or plasma was effectively blocked by the glucocorticoid receptor antagonist RU-486. Thus exercise-elicited endogenous cortisol effectively augments CXCR4 expression on T lymphocytes, which may account for lymphopenia after exercise.
Okutsu
Mitsuharu
M
Medicine and Science in Sports and Exercise, Tohoku University Graduate School of Medicine, Seiryo-machi 2-1, Aoba-ku, Sendai, 980-8575 Japan.
Ishii
Kenji
K
Niu
Kai Jun
KJ
Nagatomi
Ryoichi
R
D000208:Acute Disease; D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002465:Cell Movement; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D002634:Chemotaxis, Leukocyte; D015444:Exercise; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000494:pharmacology*; D008297:Male; D009000:Monocytes / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism*; D013312:Stress, Physiological / Q000150:complications* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D013601:T-Lymphocytes / Q000378:metabolism*; D013997:Time Factors
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019718:Receptors, CXCR4; D006854:Hydrocortisone