Extrathoracic multiple trauma dysregulates neutrophil function and exacerbates pneumonia-induced lung injury
| Autor: | Mark H. Hoofnagle, Jennifer M. Leonard, Christina X. Zhang, Anja Fuchs, Regina A. Clemens, Grant V. Bochicchio, Shin-Wen Hughes, Richard S. Hotchkiss, Liang Lu, Sarbani Ghosh, Isaiah R. Turnbull |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Myeloid Neutrophils Secondary infection Acute Lung Injury Lung injury Critical Care and Intensive Care Medicine Article 03 medical and health sciences Mice 0302 clinical medicine medicine Pneumonia Bacterial Animals Humans Pseudomonas Infections Lung Trauma Severity Indices medicine.diagnostic_test business.industry Multiple Trauma 030208 emergency & critical care medicine medicine.disease Polytrauma Pneumonia Disease Models Animal medicine.anatomical_structure Bronchoalveolar lavage Immunology Pseudomonas aeruginosa Crush injury Surgery business Reactive Oxygen Species |
| Zdroj: | J Trauma Acute Care Surg |
| ISSN: | 2163-0763 |
| Popis: | BACKGROUND Forty percent of critically ill trauma patients will develop an infectious complication. Pneumonia is the most common cause of death of trauma patients surviving their initial insult. We previously demonstrated that polytrauma (PT), defined as two or more severe injuries in at least two areas of the body, induces emergency hematopoiesis characterized by accelerated myelopoiesis in the bone marrow and increased myeloid cell frequency in the peripheral tissues. We hypothesized that PT alone induces priming of neutrophils, resulting in hyperactivation upon secondary exposure to bacteria and causing acute lung injury and increased susceptibility to secondary exposure to Pseudomonas aeruginosa pneumonia. METHODS C57BL/6 mice were subjected to PT consisting of a lower extremity pseudofracture, liver crush injury, and 15% blood-volume hemorrhage. Pneumonia was induced by intratracheal injection of 5 × 106 CFU live P. aeruginosa or 1 × 107 of heat-killed P. aeruginosa (HKPA). For reactive oxygen species (ROS), studies polymorphonuclear neutrophils (PMNs) were isolated by immunomagnetic bead negative selection and stimulated ex-vivo with HKPA. Reactive oxygen species production was measured by immunofluorescence. For histology, lung sections were stained by hematoxylin-eosin and analyzed by a blinded grader. RESULTS Polytrauma induced persistent changes in immune function at baseline and to secondary infection. Pneumonia after injury resulted in increased mortality (60% vs. 5% p < 0.01). Blood neutrophils from PT mice had higher resting (unstimulated) ROS production than in naive animals (p < 0.02) demonstrating priming of the neutrophils following PT. After intratracheal HKPA injection, bronchoalveolar lavage PMNs from injured mice had higher ROS production compared with naive mice (p < 0.01), demonstrating an overexuberant immunopathologic response of neutrophils following PT. CONCLUSION Polytrauma primes neutrophils and causes immunopathologic PMN ROS production, increased lung injury and susceptibility to secondary bacterial pneumonia. These results suggest that trauma-induced immune dysfunction can cause immunopathologic response to secondary infection and suggests neutrophil-mediated pulmonary damage as a therapeutic target for posttrauma pneumonia. |
| Databáze: | OpenAIRE |
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