title: Humic acid enhances cigarette smoke-induced lung emphysema in mice and IL-8 release of human monocytes.
abstract: Tobacco smoke is the main factor in the etiology of lung emphysema. Generally prolonged, substantial exposure is required to develop the disease. Humic acid is a major component of cigarette smoke that accumulates in smokers' lungs over time and induces tissue damage.
  
  
  OBJECTIVE
  To investigate whether humic acid pre-loading potentiates the development of cigarette smoke-induced lung emphysema in mice and increases IL-8 release by human monocytes.
  
  
  METHODS
  C57BL/6J mice received humic acid or aqueous vehicle by tracheal installation on day 0 and day 7. From day 21 to day 84, the mice were exposed to cigarette smoke or clean air for 5 days/week. Twenty-four hours after the last exposure we determined leukocytes in lung lavage, heart hypertrophy and alveolar wall destruction. Human monocytes were incubated with cigarette smoke extract (CSE), humic acid or the combination overnight.
  
  
  RESULTS
  Humic acid nor cigarette smoke caused alveolar wall destruction within two months. Interestingly, the combination did induce lung emphysema. Humic acid, cigarette smoke or the combination did not change leukocyte types and numbers in lung lavage fluid, but the combination caused peribronchiolar and perivascular lymphocyte infiltration. Humic acid treatment resulted in a high proportion of alveolar macrophages heavily loaded with intracellular granula. Humic acid also induces the release of IL-8 from human monocytes and enhances the CSE-induced IL-8 release.
  
  
  CONCLUSIONS
  Humic acid deposition in the lungs potentiates the development of cigarette smoke-induced interstitial inflammation and lung emphysema. Moreover, humic acid promotes IL-8 release from human monocytes. Since humic acid accumulates steadily in the lungs of smokers, this may provide an explanation for the natural history on late onset of this disease. The model described here offers a novel way to study emphysema and may direct the search for new therapeutic approaches.
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, The Netherlands.
authors.forename: Sven
authors.initials: S
authors.lastname: van Eijl
authors.forename: Esmaeil
authors.initials: E
authors.lastname: Mortaz
authors.forename: Ana F
authors.initials: AF
authors.lastname: Ferreira
authors.forename: Frieke
authors.initials: F
authors.lastname: Kuper
authors.forename: Frans P
authors.initials: FP
authors.lastname: Nijkamp
authors.forename: Gert
authors.initials: G
authors.lastname: Folkerts
authors.forename: Nanne
authors.initials: N
authors.lastname: Bloksma
mesh_terms: D000818:Animals; D005260:Female; D006330:Heart Defects, Congenital / Q000209:etiology; D006352:Heart Ventricles / Q000002:abnormalities; D006812:Humic Substances / Q000633:toxicity*; D016209:Interleukin-8 / Q000378:metabolism*; D008168:Lung / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D011656:Pulmonary Emphysema / Q000209:etiology* / Q000473:pathology; D017382:Reactive Oxygen Species; D012906:Smoke / Q000009:adverse effects*
chemical_list: D006812:Humic Substances; D016209:Interleukin-8; D017382:Reactive Oxygen Species; D012906:Smoke