gms | German Medical Science

Objectives: Acute respiratory distress syndrome (ARDS) is a common complication after thoracic/chest trauma causing high mortality rates. Peripheral circulating monocytes, which are rapidly recruited to inflammatory tissues, are suggested to regulate and amplify the inflammatory response. As little is known about their plasticity and dynamics, we investigated their behaviour in systemic and local inflammation after thoracic/chest trauma and during ARDS-development.

Methods: Isolated blunt chest trauma (TxT) and TxT combined with cecal ligation and puncture (CLP) causing ARDS were induced in c57BL/GN-mice. Control groups did not receive any impact. Six and 24h after surgery, peripheral blood, lung tissue and bronchoalveolar lavage fluid (BALF) were gathered. Whole blood samples were stained for viable CD45+Ly6C+Ly6G-CD11b+ monocytes, and their plasticity was determined by CD11c expression. Single cell solutions from the lung tissue were used for monocyte and CD45+Ly6CbrightF4/80+ macrophage analysis. Total protein content of the BALF was determined using Coomassie Blue. Lung tissue protein homogenates were analyzed for C-X-C motif chemokine ligand (CXCL)1 using enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed by non-parametric Kruskal-Wallis test with post-hoc Dunn's correction.

Results: A significant systemic decline of monocytes after TxT and in ARDS was observed after 6h. While in TxT there was a monocyte recovery, this decline persisted in ARDS after 24h. Correspondingly a pulmonary infiltration with CD11b+monocytes increased 6h with a recovery at 24h after TxT, but persisted at increased levels in ARDS. The percentage of inflammation-associated CD11cbrightLy6G-CD11b+monocytes was significantly increased during ARDS after 6h and even further after 24h systemically and in lungs. The increase of Ly6CbrightF4/80+macrophages was most prominent 24h after ARDS. In both groups CXCL1 was significantly enhanced, however, the strongest expression was observed 24h after ARDS-induction. Lung damage was correspondingly increased in both TxT and ARDS group after 6h. While lung damage was decreased in TxT, it remained high in ARDS after 24h.

Conclusion: Peripheral inflammation-associated monocytes emigrate and in parallel, inflammation-associated macrophages are increased in lungs after TxT and ARDS. However, while TxT-caused changes recover after 24h, during ARDS there is still a significant maintenance of these cell-types systemically and locally. Persisting local CXCL1 expression is associated with enhanced monocyte/macrophage activation in lungs, all together contributing to lung damage and ARDS development. The changes in the plasticity of monocytes/macrophages are partly caused by the isolated TxT alone, and do not necessarily mirror the ARDS-development. A differential view on ARDS-models requires considering of specific control groups.

This project was funded by the DFG WU 820/2-1, HI 820/5-1, RE 3304/8-1