Targeting Glutamate transport: A breakthrough in mitigating sepsis lung injury.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) can result from various factors, including sepsis, one of the high-risk causes of ALI/ARDS. Recent research emphasizes the role of Glutamate metabolism in ALI/ARDS. Our study found a strong correlation between the difference in serological Glutamate levels of arterial vs venous blood and the progression of lung injury. High arterial - venous (A-V) Glutamate discrepancies were significantly associated with severity in ALI/ARDS patients. Additionally, the subunit of Glutamate transporter system XC- was notably elevated in mouse lungs affected by sepsis and LPS-induced macrophages. Pharmacological inhibition of system XC- or knocking down xCT worsened sepsis-related lung injury in mice. We also showed that xCT in macrophages is essential for activating system XC- for Glutamate transport, offering protection against sepsis-related ALI. Our findings highlight the therapeutic potential of Glutamate transport in mitigating lung injury and provide a promising approach for predicting ALI/ARDS prognosis.