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2010
Journal Article
Titel
Adjuvant activity of carbon black particles in a mouse model of allergic asthma - characterization of particle loaded cells and their fate upon inhalation
Titel Supplements
Abstract
Abstract
RATIONALE: Human and animal studies reveal that exposure to various particulate matter (PM) induces exacerbation of asthmatic airway inflammation. Although adjuvant activity of PM is well known, cellular mechanisms behind this phenomenon are still under-researched. METHODS: Balb/c mice are intranasally exposed either to OVA or combined with CBP during sensitization on day 0, 1, 2 and challenged with OVA on days 14, 15 and 18, 19. Induction of allergic airway inflammation and adjuvant activity of CBP were studied in lung and mediastinal lymph nodes (mLN) on day 21 by means of bronchoalveolar lavage (BAL), cytokine assays, lung function and histology. To clarify which cells take up CBP in lung and mLN, we performed iterative-chip-based-cytometry (iCBC) of these organs. RESULTS: Total cell count and differential cell counts in BAL increased significantly in mice sensitized with OVA combined with CBP. Additionally, lung function decreased and OVA specific IgG2A and IgE levels increased in serum. Alongside, exposure to CBP increases proinflammatory mediators in BAL. iCBC revealed that cells phagocytozing CBP are negative for CD205, B220, Gr-1, but positive for CD11b, CD11c. Particle loaded cells in lung show heterogeneous expression of costimulatory molecules compared to those in the mLN disclosing differences in their activation status. CONCLUSIONS: Our results show that phagocytosis of CBP in the lung and transportation of these to mLN is mediated by cells with a distinct morphology and activation status. These date provide a basis for manipulation of these cells which will disclose underlying mechanisms of the adjuvant activity of CBP.