title: Age-dependent alterations of monocyte subsets and monocyte-related chemokine pathways in healthy adults.
abstract: BACKGROUND
  Recent experimental approaches have unraveled essential migratory and functional differences of monocyte subpopulations in mice. In order to possibly translate these findings into human physiology and pathophysiology, human monocyte subsets need to be carefully revisited in health and disease. In analogy to murine studies, we hypothesized that human monocyte subsets dynamically change during ageing, potentially influencing their functionality and contributing to immunosenescence.
  
  
  RESULTS
  Circulating monocyte subsets, surface marker and chemokine receptor expression were analyzed in 181 healthy volunteers (median age 42, range 18-88). Unlike the unaffected total leukocyte or total monocyte counts, non-classical CD14+CD16+ monocytes significantly increased with age, but displayed reduced HLA-DR and CX(3)CR1 surface expression in the elderly. Classical CD14++CD16- monocyte counts did not vary dependent on age. Serum MCP-1 (CCL2), but not MIP1alpha (CCL3), MIP1beta (CCL4) or fractalkine (CX(3)CL1) concentrations increased with age. Monocyte-derived macrophages from old or young individuals did not differ with respect to cytokine release in vitro at steady state or upon LPS stimulation.
  
  
  CONCLUSIONS
  Our study demonstrates dynamic changes of circulating monocytes during ageing in humans. The expansion of the non-classical CD14+CD16+ subtype, alterations of surface protein and chemokine receptor expression as well as circulating monocyte-related chemokines possibly contribute to the preserved functionality of the monocyte pool throughout adulthood.
authors.affiliation: Department of Medicine III, University Hospital, RWTH-Aachen, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Seidler
authors.forename: Henning W
authors.initials: HW
authors.lastname: Zimmermann
authors.forename: Matthias
authors.initials: M
authors.lastname: Bartneck
authors.forename: Christian
authors.initials: C
authors.lastname: Trautwein
authors.forename: Frank
authors.initials: F
authors.lastname: Tacke
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood / Q000276:immunology*; D002465:Cell Movement; D018932:Chemokine CCL2 / Q000097:blood; D018925:Chemokines / Q000097:blood / Q000276:immunology*; D015331:Cohort Studies; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism; D006262:Health; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D019707:Receptors, Chemokine / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D055815:Young Adult
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018925:Chemokines; D006684:HLA-DR Antigens; D018950:Lipopolysaccharide Receptors; D019707:Receptors, Chemokine; D017452:Receptors, IgG