Stress-Induced Eosinophil Activation Contributes to Postoperative Morbidity and Mortality After Lung Resection

Infectious Diseases Medicine Respiratory System Basic Medical Sciences Life Sciences Immunology
stress eosinophils lung resection postoperative complications lung injury

Research Background

With global population aging, the number of lung resection surgeries has increased significantly, including primary lung cancer resection, removal of lung metastases, and surgeries to treat lung infections or emphysema. However, little is known about the systemic stress response after thoracic surgery and interventions to improve post-lung resection rehabilitation. The incidence of pulmonary complications after lung resection is as high as 50%, with many patients not requiring oxygen therapy before surgery but needing prolonged oxygen supplementation afterward. These complications not only prolong hospital stays and affect recovery but can also lead to lung failure in severe cases.

Although acute respiratory distress syndrome after surgery was reported as early as 1942, its etiology remains unclear. Some studies have suggested that excessive fluid infusion or overventilation during surgery may be triggering factors, but these theories are also controversial. Research has shown that high-dose corticosteroids can improve postoperative outcomes, suggesting that inflammation may play an important role.

Paper Source

This paper, titled “Stress-induced eosinophil activation contributes to postoperative morbidity and mortality after lung resection,” was published in Science Translational Medicine on August 21, 2024. The authors include Zhongcheng Mei, May A. Khalil, Yizhan Guo, and others from institutions such as the University of Maryland, University of Pittsburgh, Washington University, and Mayo Clinic.

Detailed Description of Research Process

Research Subjects and Experimental Procedures:

This study used a mouse lung resection model and peripheral blood samples from patients undergoing lung or abdominal surgery to explore the mechanisms of lung tissue damage, non-cardiogenic pulmonary edema, hypoxemia, and death caused by proinflammatory circulation induced by lung surgery.

  1. Mouse Experiments:

    • Used mouse models for left and right lung resection surgeries, collecting postoperative blood, right lung, and spleen samples.
    • Analyzed white blood cells, especially changes in eosinophils, in blood and tissues using flow cytometry.
    • Evaluated eosinophil generation and maturation processes in bone marrow.

  2. Patient Sample Analysis:

    • Collected peripheral blood samples from patients undergoing lung resection or abdominal surgery.
    • Analyzed changes in peripheral blood eosinophil percentages at different time points before and after surgery.

Experimental Results:

  1. Lung Resection Induces Eosinophil Activation and Systemic Increase:

    • In mouse models, after left lung resection, the proportion of eosinophils in blood, right lung, and spleen increased significantly.
    • Similarly, in patients undergoing lung resection, the proportion of eosinophils in blood increased significantly, but no similar changes were observed in patients undergoing abdominal surgery.

  2. Lung Resection Induces Pulmonary Eosinophil Activation and Accelerated Eosinophil Maturation in Bone Marrow:

    • In mouse models, after left lung resection, eosinophils in the right lung showed activation markers such as upregulation of CD69 and iNOS.
    • The number of mature eosinophils in bone marrow increased, while the number of precursor cells did not change significantly, suggesting accelerated eosinophil maturation.

  3. Inhibition of Eosinophils Improves Postoperative Prognosis:

    • In the right lung resection model, mice with specific depletion of eosinophils had significantly higher survival rates and faster weight recovery.
    • Similarly, mice treated with anti-CCR3 or anti-Siglec-F antibodies showed improved survival rates, reduced pulmonary edema, and improved hypoxemia after right lung resection.

  4. Key Role of IL-7 in Eosinophil Maturation in Bone Marrow:

    • After lung resection, IL-7 concentrations in bone marrow increased significantly. Using IL-7 neutralizing antibodies or IL-7 receptor-deficient mice inhibited eosinophil maturation.
    • IL-7 is mainly produced by γδT cells after lung resection, and depletion of γδT cells significantly downregulated IL-7 expression, inhibiting eosinophil maturation and activation.

  5. Role of ILC2 in IL-7-Mediated Eosinophil Activation:

    • Depletion of ILC2 inhibited eosinophil activation and maturation in bone marrow.
    • ILC2 mediated IL-7 signaling through GM-CSF, promoting eosinophil activation and lung injury.

Conclusions and Research Significance:

The study indicates that lung resection-induced stress response promotes GM-CSF-dependent eosinophil expansion and activation through IL-7-mediated ILC2 activation, ultimately leading to iNOS production and lung tissue damage.

  • Scientific Value: This study reveals a novel inflammatory pathway after lung resection surgery, elucidating the role of the IL-7/ILC2/GM-CSF/eosinophil axis in mitochondrial stress and lung injury.
  • Application Value: Targeting existing FDA-approved drugs for eosinophil activation or neutralizing NOS during the perioperative period may provide new approaches to improve postoperative prognosis in high-risk patients.

Research Highlights

  1. Novel Research Perspective: Reveals potential inflammatory mechanisms of postoperative lung injury.
  2. Multidisciplinary Collaboration: Multiple authors from different research fields and institutions demonstrate the importance of interdisciplinary cooperation.
  3. Translational Medicine Potential: Research results support intervention in postoperative complications through existing drugs, providing new ideas for clinical treatment.