title: Serum chitotriosidase, a putative marker of chronically activated macrophages, increases with normal aging.
abstract: BACKGROUND
  Chitotriosidase (ChT) is secreted by chronically activated macrophages in Gaucher's disease. We hypothesize that circulating levels of ChT are altered with normal aging, reflecting age-related chronic macrophage activation. Potential sources that might contribute to altered levels were assessed by measuring systemic levels of ChT are α-naphthyl acetate esterase, a macrophage lysosomal enzyme; granulocyte-macrophage colony-stimulating factor (GM-CSF), which stimulates neutrophilic granule release of ChT; interleukin-6 (IL-6); and neopterin, a macrophage activation marker.
  
  
  METHODS
  Serum was obtained from 315 healthy participants whose age ranged from 18 to 92 years. Anthropometric measures included percent body fat and body mass index. ChT and α-naphthyl acetate esterase levels were measured by enzyme activity assays. GM-CSF, IL-6, and neopterin concentrations were measured by commercial enzyme-linked immunosorbent assays. Serum marker values were statistically analyzed using nonparametric tests.
  
  
  RESULTS
  Six percent of the participants had undetectable ChT levels. A positive association with age was observed for ChT and IL-6, whereas a negative correlation with age was seen for α-naphthyl acetate esterase and GM-CSF. ChT values were not associated with α-naphthyl acetate esterase or GM-CSF levels. ChT was independently associated with IL-6 and neopterin levels, but statistical significance was attenuated when controlled for age.
  
  
  CONCLUSIONS
  The data are consistent with increased serum ChT activity not arising from altered macrophage lysosomal enzyme trafficking or GM-CSF-stimulated release of neutrophil granule stores. The association of ChT with age remains significant after controlling for neopterin and IL-6 changes with age, suggesting that ChT levels reflect a macrophage state distinct from acute macrophage activation or inflammatory state.
authors.affiliation: Room 1A12 JHAAC, 5501 Hopkins Byview Circle, Baltimore, MD 21224. nfedark1@jhmi.edu.
authors.forename: Rohit
authors.initials: R
authors.lastname: Ramanathan
authors.forename: Anita
authors.initials: A
authors.lastname: Kohli
authors.forename: María Clara
authors.initials: MC
authors.lastname: Ingaramo
authors.forename: Alka
authors.initials: A
authors.lastname: Jain
authors.forename: Sean X
authors.initials: SX
authors.lastname: Leng
authors.forename: Naresh M
authors.initials: NM
authors.lastname: Punjabi
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Walston
authors.forename: Neal S
authors.initials: NS
authors.lastname: Fedarko
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood* / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood; D006596:Hexosaminidases / Q000097:blood*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008262:Macrophage Activation; D008297:Male; D008875:Middle Aged; D009283:Naphthol AS D Esterase / Q000097:blood; D019798:Neopterin / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D019798:Neopterin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D009283:Naphthol AS D Esterase; D006596:Hexosaminidases; C086400:chitotriosidase
keywords: Biomarkers; Blood; Inflammation; Macrophage