title: Elastases from inflammatory and dendritic cells mediate ultrafine carbon black induced acute lung destruction in mice.
abstract: BACKGROUND
  Exposure to ultrafine particles (<100 nm in diameter) is postulated to cause chronic obstructive pulmonary disease (COPD). However, the mechanism remains to be elucidated.
  
  
  OBJECTIVE
  We aimed to evaluate whether ultrafine particle exposure causes the infiltration of inflammatory and dendritic cells (DCs) with increased elastase activity, contributing to lung parenchymal destruction.
  
  
  METHODS
  C57BL/6 male mice were intratracheally instilled with 300 µg ultrafine carbon black (ufCB; 14 nm in diameter), and sacrificed at 1, 3, 7 and 14 d post-exposure. Differential cell counts, elastase activities, and desmosine and hydroxyproline in bronchoalveolar (BAL) fluid were determined. Immunofluorescent staining and flow cytometry analysis determined the cell origin of macrophage metalloelastase (MMP-12). Anti-neutrophil antibody was applied to assess the contribution of elastase in ufCB induced lung destruction.
  
  
  RESULTS
  ufCB exposure led to significant increases in neutrophils, mononuclear cells and total proteins in BAL fluid. Desmosine and hydroxyproline were significantly increased in the ufCB group. Elastase activities were found to be significantly elevated, with both neutrophil elastase and MMP-12 peaking at 3 d post-exposure. Flow cytometry analysis demonstrated that pulmonary infiltrations of MMP-12 positive DCs, including Langerhans cells-derived DCs, occurred at 3 d and 7 d, while macrophage infiltration was obvious starting at 1 d. Anti-neutrophil antibody significantly reduced neutrophil elastase activity and prevented the increases in BAL desmosine and hydroxyproline following ufCB exposure.
  
  
  CONCLUSIONS
  For the first time we demonstrate the infiltration of Langerhans and myeloid dendritic cells, and show that elastase production contributes to pulmonary destruction following exposure to ultrafine particles.
authors.affiliation: Department of Environmental and Occupational Health, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Chih-Ching
authors.initials: CC
authors.lastname: Chang
authors.forename: Chin-Yu
authors.initials: CY
authors.lastname: Chen
authors.forename: Hui-Fen
authors.initials: HF
authors.lastname: Chiu
authors.forename: Shi-Xun
authors.initials: SX
authors.lastname: Dai
authors.forename: Ming-Yie
authors.initials: MY
authors.lastname: Liu
authors.forename: Chun-Yuh
authors.initials: CY
authors.lastname: Yang
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D000393:Air Pollutants / Q000032:analysis / Q000633:toxicity*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D003094:Collagen / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D004547:Elastic Tissue / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D019570:Inhalation Exposure / Q000009:adverse effects; D019272:Leukocyte Elastase / Q000378:metabolism*; D007962:Leukocytes / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D008297:Male; D053508:Matrix Metalloproteinase 12 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D010316:Particle Size; D053260:Soot / Q000032:analysis / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D053260:Soot; D003094:Collagen; D019272:Leukocyte Elastase; D053508:Matrix Metalloproteinase 12