title: Mast cells play a critical role in the systemic inflammatory response and end-organ injury resulting from trauma.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Department of Hepatobiliary Surgery, Qingdao University Medical School Hospital, Qingdao, China.
authors.forename: Changchun
authors.initials: C
authors.lastname: Cai
authors.forename: Zongxian
authors.initials: Z
authors.lastname: Cao
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Loughran
authors.forename: Sodam
authors.initials: S
authors.lastname: Kim
authors.forename: Sophie
authors.initials: S
authors.lastname: Darwiche
authors.forename: Sebastian
authors.initials: S
authors.lastname: Korff
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Billiar
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D004247:DNA / Q000097:blood; D004195:Disease Models, Animal; D005264:Femoral Fractures / Q000276:immunology / Q000473:pathology; D005455:Fluorescent Antibody Technique; D024243:HMGB1 Protein / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000473:pathology*; D008168:Lung / Q000473:pathology*; D008262:Macrophage Activation; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009336:Necrosis / Q000276:immunology; D012771:Shock, Hemorrhagic / Q000276:immunology / Q000473:pathology; D017695:Soft Tissue Injuries / Q000276:immunology / Q000473:pathology; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015415:Biomarkers; D024243:HMGB1 Protein; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D004247:DNA; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase