Neurogenic pulmonary edema (NPE) is a complication that often affects patients following central nervous system (CNS) injury. Nevertheless, the complex relationship between CNS injury and NPE initiation and progression remains unclear. Here, we show that the leakage of brain proteins (BPs) following traumatic brain injury results in the formation of immune complexes and lung edema. Quantitative proteomic analysis revealed that BP preferentially affected the Kng1/SPHK2/S1P pathway. We treated rats with the S1P receptor antagonist fingolimod or conventional steroid drugs and showed that this was sufficient to attenuate the severity of pulmonary and related pathological changes. These results provide novel evidence that the immune complexes induced by BPs are deposited in the lung tissue, activating a series of inflammatory reactions that culminate in pulmonary edema. Considering these results, we propose the innovative concept of “neuroimmunogenic pulmonary edema” as a relevant pathological entity.
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