Mast Cells Play a Critical Role in the Systemic Inflammatory Response and End-Organ Injury Resulting from Trauma

作者：Cai, Changchun; Cao, Zongxian; Loughran, Patricia A.; Kim, Sodam; Darwiche, Sophie; Korff, Sebastian; Billiar, Timothy R.^*

来源：Journal of the American College of Surgeons, 2011, 213(5): 604-615.

DOI：10.1016/j.jamcollsurg.2011.08.009

• MEDIATES HEPATIC-INJURY
• ACUTE LUNG INJURY
• HEMORRHAGIC-SHOCK
• MITOCHONDRIAL-DNA
• IMPROVES SURVIVAL
• SEVERITY
• MODEL
• CHEMOKINES
• SEPSIS
• HMGB1

BACKGROUND: Much of the morbidity after trauma results from excessive activation of the innate immune system. This is manifested as a systemic inflammatory response and associated end-organ damage. Although mast cells are known to be important in many immune responses, their role in the systemic response to severe trauma is unknown.
STUDY DESIGN: C57BL/6J-KitW-sh/BsmJ (mast cell deficient) and wild type mice were subjected to 1.5 hours of hemorrhagic shock plus bilateral femur fracture and soft tissue injury (HS/T), followed by resuscitation at 4.5 hours. Blood withdrawal volumes, mean arterial pressures, circulating cytokine, chemokine, high mobility group box-1 (HMGB-1), double strain DNA (dsDNA), transaminase levels, and histology in liver and lung were compared between groups.
RESULTS: Mast cell deficient mice exhibited greater hemodynamic stability than wild type mice. At baseline, the mast cell deficient mice exhibited no difference in any of the organ injury or inflammatory markers measured. As expected, wild type mice subjected to HS/T exhibited end-organ damage manifested by marked increases in circulating alanine transaminase, aspartate aminotransferase, and dsDNA levels, as well as histologic evidence of tissue necrosis. In clear contrast, mast cell deficient mice exhibited almost no tissue damage. Similarly, the magnitude of increased circulating cytokine and chemokine induced by HS/T was much less in the mast cell deficient mice than in the wild type group.
CONCLUSIONS: Mast cell deficiency resulted in a damped systemic inflammatory response, greatly attenuated multiple organ injury, and more stable hemodynamics in HS/T. So mast cells appear to be a critical component of the initial host response to severe injury. (J Am Coll Surg 2011;213:604-615.

• 出版日期2011-11
• 单位青岛大学