The Mechanism Of Mitochondrial DAMPs From Fracture On The Lung Infection In Multiple Trauma

Objective: Lung infection is a common complication of multiple trauma patients, andfracture is the most common injury type. Previous studies have shown that fractureincreased the incidence of lung infections in multiple trauma patients. However, themechanism was not fully understood between fracture and lung infections. We have foundthat femoral reamings released mitochondrial damage-associated molecular patterns(Damage Associated Molecular Patterns, DAMPs). Studies have shown that themitochondria and bacterial was homologous, and kept some characteristics of bacteria.Formyl peptides synthetied by bacteria can activate neutrophil by the formyl peptidereceptor (formyl peptide receptor, FPR). Neutrophil was the key cell in inflammation, andit was very important for the removal of invading microbes. Therefore, this study willfocus on the effect of mitochondrial DAMPs from fracture and neutrophils on the lunginfection in multiple trauma.Meitiods: Observe the effect of the mitochondria DAMPs from fracture on theneutrophils through in vitro experiments. Establish multiple trauma animal model with themitochondria DAMPs from fracture and pulmonary contusion. Count the number ofneutrophil in BALF and test the concentration of myeloperoxidase (Myeloperoxidase,MPO) in lung tissue. Observe the effects of mitochondrial DAMPs from the fractures onthe distribution of neutrophils in lung for the multiple trauma. Injections bacteria into thelung atfer the animal pretreated with the mitochondrial DAMPs from the fractures, andobserve whether the mitochondrial DAMPs from the fractures will potentially leaving thelung susceptible to infection.Results: Mitochondrial DAMPs from fracture caused brisk PMN Ca2+flux, and responses were inhibited by using anti-FPR (formyl peptide receptor)1or anti-FPR2invitro experiments. In the multiple trauma animal models, we can see the neutrophilsaccumulation in the damage area of the lung tissue,however, the number of neutrophils inbronchoalveolar lavage fluid was significantly decreased due to the mitochondrial DAMPsfrom the fracture. Further, we found that the bacteria increased a lot if the animalpretreated with the mitochondrial DAMPs from the fracture.Conclusions: Mitochondrial DAMPs from fracture decreased the ability ofneutrophils acrossing into the pulmonary alveoli by activation of FPRl and FPR2, andtherefore it potentially caused the lung susceptible to infection.