Differential TNF production by monocyte subsets under physical stress: blunted mobilization of proinflammatory monocytes in prehypertensive individuals
Stoyan Dimitrov, Farah Shaikh, Christopher Pruitt, Michael Green, Kathleen Wilson, Nuzhat Beg and Suzi Hong
Brain, behavior, and immunity, v 27(1), pp 101-108
Adult Case-Control Studies Cell Differentiation - drug effects Cell Differentiation - immunology Cell Movement - drug effects Cell Movement - immunology Down-Regulation Exercise - physiology Exercise Test Female Flow Cytometry GPI-Linked Proteins - drug effects GPI-Linked Proteins - immunology HLA-DR Antigens - immunology Humans Isoproterenol - pharmacology Lipopolysaccharide Receptors - immunology Lipopolysaccharides - immunology Lipopolysaccharides - pharmacology Male Monocytes - cytology Monocytes - drug effects Monocytes - immunology Prehypertension - immunology Receptors, Adrenergic - drug effects Receptors, Adrenergic - immunology Receptors, IgG - drug effects Receptors, IgG - immunology Sympathomimetics - pharmacology Tumor Necrosis Factor-alpha - drug effects Tumor Necrosis Factor-alpha - immunology
Elevated blood pressure (BP) and infiltration of the vasculature by monocytes contribute to vascular pathology; but, monocyte migratory characteristics based on differing inflammatory potential under adrenergic activation remains unclear. We compared nonclassical (CD14(+)CD16(++); HLA-DR(+)), intermediate (CD14(++)CD16(+); HLA-DR(++)), and classical (CD14(++)CD16(-); HLA-DR(+/-)) monocyte trafficking and their LPS-stimulated TNF production in response to a physical stressor (20-min treadmill exercise at 65-70% VO(2peak)) in participants with high prehypertension (PHT), mild PHT or normal BP (NBP). To determine adrenergic receptor (AR) sensitivity, pre-exercise cells were also treated with isoproterenol (Iso). When cells were stimulated with LPS, the CD16 molecules were downregulated, and monocyte subsets were differentiated based on HLA-DR expression. Monocyte subpopulations (as % of total monocytes) and intracellular TNF production were evaluated by flow cytometry. TNF production in all subsets decreased post-exercise and with ex-vivo incubation with Iso, irrespective of BP (p<0.001), with nonclassical and intermediate monocytes being a major source of TNF production. Overall, % nonclassical monocytes increased, % intermediate did not change, whereas % classical decreased post-exercise (p<0.001). However, % increase in nonclassical monocytes under exercise-induced adrenergic activation was blunted in high PHT individuals (p<0.05), but not in individuals with mild PHT and NBP. These findings extend our previous reports by showing that the mobilization of proinflammatory monocytes under physical stress is attenuated with even mild BP elevation. This may be indicative of monocytic AR desensitization and/or greater adhesion of "proinflammatory" monocytes to the vascular endothelium in hypertension with potential clinical implications of vascular pathology.
Differential TNF production by monocyte subsets under physical stress: blunted mobilization of proinflammatory monocytes in prehypertensive individuals
Creators
Stoyan Dimitrov - University of California San Diego
Farah Shaikh
Christopher Pruitt
Michael Green
Kathleen Wilson
Nuzhat Beg
Suzi Hong
Publication Details
Brain, behavior, and immunity, v 27(1), pp 101-108