Are you Stefanie Mangold?

Claim your profile

Publications (4)2.87 Total impact

  • Source
    Stefanie Mangold
    [Show abstract] [Hide abstract]
    ABSTRACT: Alveolar type 2 (AT2) cell apoptosis is an important mechanism during lung inflammation, lung injury and regeneration. Blunt chest trauma has been shown to activate inflammatory cells such as alveolar macrophages (AM) or neutrophils (PMN), resulting in an inflammatory response. The present study was performed to determine the capacity of different components / cells of the alveolar compartment like AM to induce apoptosis in AT2 cells following blunt chest trauma. To study this, male Sprague Dawley rats were subjected to either sham procedure or blunt chest trauma induced by a single blast wave. Various time points after injury (6 h - 7 d) lungs were analyzed by immunohistochemistry, stained with an anti-cytokeratin-antibody (clone MNF-116) as AT2 cell marker or antibodies directed against Caspase 3, Caspase 8, Fas, Fas ligand (FasL), BAX and BCL-2. BAL-concentrations of Fas Ligand and IL-1b were determined by ELISA. Furthermore, cultures of AT2 cells isolated from healthy rats were incubated with supernatants of AM obtained from either trauma or sham operated animals in the presence or absence of H2O2. Annexin 5 stain and TUNEL assay were used to detect apoptotic events in AT2 cells. Histological evaluation revealed that the totality of AT2 cells was significantly reduced at 48 hours following trauma. Fas, FasL, active Caspase 8 and active Caspase 3 were markedly up regulated in AT2 cells after chest trauma. BAX and BCL-2 did not show any changes between sham and trauma. In BAL fluids, IL-1b and FasL were markedly increased at 24 hours after injury. The apoptosis rate of AT2 cells incubated with supernatants from cultured AM, isolated at 48 hours following chest trauma or sham procedure, was markedly increased when compared to shams. In summary, blunt chest trauma induced apoptosis in AT2 cells via the extrinsic death receptor pathway (Fas/ FasL). Furthermore, mediators released by AM appeared to be involved in the induction of programmed cell death in AT2 cells.
    01/2009;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Alveolar type 2 (AT-2) cell apoptosis is an important mechanism during lung inflammation, lung injury, and regeneration. Blunt chest trauma has been shown to activate inflammatory cells such as alveolar macrophages (AMs) or neutrophils (polymorphonuclear granulocytes [PMNs]), resulting in an inflammatory response. The present study was performed to determine the capacity of different components/cells of the alveolar compartment (AMs, PMNs, or bronchoalveolar lavage [BAL] fluids) to induce apoptosis in AT-2 cells following blunt chest trauma. To study this, male Sprague-Dawley rats were subjected to either sham procedure or blunt chest trauma induced by a single blast wave. Various time points after injury (6 h to 7 d), the lungs were analyzed by immunohistochemistry, for AT-2 cells, or with antibodies directed against caspase 3, caspase 8, Fas, Fas ligand (FasL), BAX, and BCL-2. Bronchoalveolar lavage concentrations of TNF-alpha, IL-1beta, and soluble FasL were determined by enzyme-linked immunosorbent assay. Furthermore, cultures of AT-2 cells isolated from healthy rats were incubated with supernatants of AMs, PMNs, or BAL fluids obtained from either trauma or sham-operated animals in the presence or absence of oxidative stress. Annexin V staining or TUNEL (terminal deoxynucleotidyl transferase) assay was used to detect apoptotic AT-2 cells. Histological evaluation revealed that the total number of AT-2 cells was significantly reduced at 48 h following trauma. Fas, FasL, active caspase 8, and active caspase 3 were markedly up-regulated in AT-2 cells after chest trauma. BAX and BCL-2 did not show any significant changes between sham and trauma. IL-1beta, but not TNF-alpha, levels were markedly increased at 24 h after the injury, and soluble FasL concentrations were significantly enhanced at 6, 12, 24, and 48 h after the insult. Apoptosis of AT-2 cells incubated with supernatants from cultured AMs, isolated at 48 h following chest trauma was markedly increased when compared with shams. In contrast, no apoptosis was induced in AT-2 cells incubated with supernatants of activated PMNs or BAL fluids of traumatized animals. In summary, blunt chest trauma induced apoptosis in AT-2 cells, possibly involving the extrinsic death receptor pathway. Furthermore, mediators released by AMs appeared to be involved in the induction of AT-2 cell apoptosis.
    Shock (Augusta, Ga.) 03/2008; 30(5):537-44. · 2.87 Impact Factor
  • Shock. 01/2006; 26:18-19.
  • Shock. 01/2006; 25.