Auswirkungen eines stumpfen Thoraxtraumas auf die Fas/Fas-Ligand induzierte Inflammationsreaktion der Alveolar-Typ 2 Epithelzellen und Alveolarmakrophagen, sowie deren Phagozytoseaktivität
Pulmonary contusion caused by blunt chest trauma is frequently followed by acute respiratory distress syndrome, pneumonia or sepsis. Previous studies showed inflammatory alterations, pulmonary invasion of short-lived polymorphonuclear neutrophils (PMN) and apoptosis of alveolar type 2 (AT2) epithelial cells after blunt chest trauma. We hypothesized that apoptosis of AT2 cells following blunt chest trauma is mainly controlled by alveolar macrophages, that soluble Fas-ligand induces additional secretion of proinflammatory cytokines in AMphi and AT2 cells and, that the phagocytic and efferocytic response of AMphi is altered by blunt chest trauma. Furthermore we hypothesized that hydrogen sulfide (H2S) has an amplifying effect on the phagocytic activity of AMphi. The protein expression of Fas and FasL was down-regulated on the surface of AMphi, but unchanged on AT2 cells after blunt chest trauma. The mRNA expression of Fas increased in AMphi and AT2 cells. AMphi stimulated with soluble FasL (sFasL) secreted enhanced concentrations of pro-inflammatory cytokins while sFasL induced in AT2 cells a concentration dependent apoptosis but didn’t affect the cytokine release. Unstimulated AMphi isolated at 2 h after trauma ingested significantly more apoptotic AT2 cells than AMphi of sham animals. AMphi engulfing latex beads released higher levels of TNF-alpha, MIP-1alpha and CINC-1, whereas AMphi engulfing apoptotic cells released lower levels of IL-1beta and MIP-1alpha. In vivo, AMphi phagocytosis of latex beads was decreased in traumatized rats. Inhalation of H2S didn’t affect the phagocytosis of opsonized beads. These results indicate that the Fas/FasL system is activated after chest trauma and sFasL is associated with the inflammatory response after lung contusion. Pulmonary contusion causes augmentation of the alveolar macrophages efferocytosis activity. The data emphasize the important role of phagocytosis during posttraumatic inflammation after lung contusion.
Erstellung / Fertigstellung
Normierte SchlagwörterAlveolarphagozyt [GND]
Fas ligand protein [MeSH]
Macrophages, alveolar [MeSH]
Thoracic injuries [MeSH]