title: Differential TNF production by monocyte subsets under physical stress: blunted mobilization of proinflammatory monocytes in prehypertensive individuals.
abstract: 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.
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093-0804, USA.
authors.forename: Stoyan
authors.initials: S
authors.lastname: Dimitrov
authors.forename: Farah
authors.initials: F
authors.lastname: Shaikh
authors.forename: Christopher
authors.initials: C
authors.lastname: Pruitt
authors.forename: Michael
authors.initials: M
authors.lastname: Green
authors.forename: Kathleen
authors.initials: K
authors.lastname: Wilson
authors.forename: Nuzhat
authors.initials: N
authors.lastname: Beg
authors.forename: Suzi
authors.initials: S
authors.lastname: Hong
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D015536:Down-Regulation; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test; D005260:Female; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000187:drug effects / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology*; D008297:Male; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D058246:Prehypertension / Q000276:immunology*; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000276:immunology; D017452:Receptors, IgG / Q000187:drug effects / Q000276:immunology; D013566:Sympathomimetics / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000276:immunology*
chemical_list: C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D006684:HLA-DR Antigens; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D011941:Receptors, Adrenergic; D017452:Receptors, IgG; D013566:Sympathomimetics; D014409:Tumor Necrosis Factor-alpha; D007545:Isoproterenol