Mac-1/ICAM-1-dependent trogocytosis contributes to ICAM-1 neutrophils-induced lung injury in traumatic brain injury.

The lung is the most vulnerable organ following traumatic brain injury (TBI) and lung injury is closely associated with poor prognosis in patients. Recent studies have highlighted the role of neutrophils with high ICAM-1 expression (ICAM-1) in lung injury. These cells exhibit enhanced migration capacity and pro-inflammatory functions, might play a major role in the development of acute pulmonary failure following brain injury. This study aimed to investigate the potential role of ICAM-1 neutrophils in TBI-induced lung injury and elucidate the underlying mechanisms of ICAM-1 phenotype formation. In the TBI rat model, we found that a large number of neutrophils with ICAM-1 phenotype and upregulated neutrophil elastase were present not only in the contused brain but also in the injured lungs. Further analysis in vitro model revealed that trogocytosis, a Mac-1/ICAM-1-dependent process by which neutrophils capture membrane fragments containing ICAM-1 from contacted endothelial cells, contributes to neutrophils acquiring the ICAM-1 phenotype. Moreover, we found that S100B, significantly elevated in TBI rat serum, can induce the ICAM-1 expression in endothelial cells and facilitate the trogocytosis between neutrophils and endothelial cells in a Mac-1/ICAM-1-dependent manner. Finally, we found that both ICAM-1 blockade and S100B inhibition significantly reduce the number of ICAM-1 neutrophils in the lungs and alleviated lung injury following TBI. Taken together, these results suggest that by targeting S100B and Mac-1/ICAM-1-dependent trogocytosis, it may be an effective therapeutic potential to reduce the population of ICAM-1 neutrophils and thus improve lung injury after TBI.