Direct Airway Instillation of Neutrophils Overcomes Chemotactic Deficits Induced by Injury
| Autor: | Quanzhi Zhang, Leo E. Otterbein, Barbora Konečná, Garry Douglas, Barbora Vlková, Woon Yong Kwon, Jinbong Park, Elzbieta Kaczmarek, Kiyoshi Itagaki, Carl J. Hauser, Hyo In Kim, Françoise Jung, Ingred Riça |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Neutrophils 030204 cardiovascular system & hematology Critical Care and Intensive Care Medicine medicine.disease_cause Peripheral blood mononuclear cell Formyl peptide receptor 1 Article 03 medical and health sciences Mice 0302 clinical medicine medicine Pneumonia Bacterial Animals Humans Lung business.industry 030208 emergency & critical care medicine Chemotaxis medicine.disease Transplantation Mice Inbred C57BL Pneumonia Chemotaxis Leukocyte medicine.anatomical_structure Staphylococcus aureus Immunology Emergency Medicine Wounds and Injuries Wound healing business |
| Zdroj: | Shock |
| ISSN: | 1540-0514 |
| Popis: | Background Trauma induces neutrophil migration toward injury sites, both initiating wound healing and protecting against local bacterial infection. We have previously shown that mitochondrial formyl peptides (mtFPs) released by injured tissues act as chemoattractants by ligating neutrophil (PMN) formyl peptide receptor 1 (FPR1). But this process can also internalize multiple neutrophil chemoattractant receptors and thus might limit neutrophil migration to the lung in response to bacteria. Our objective was to better understand susceptibility to pneumonia after injury and thus find ways to reverse it. Methods and results We modeled the alveolar chemotactic environment in pulmonary infections by incubating Staphylococcus aureus or Escherichia coli with peripheral blood mononuclear cells (PBMC). Survey of the chemotactic mediators in the resultant conditioned media (CM) showed multiple potent chemoattractants. Pretreating PMN with mtFPs to mimic injury potently reduced net migration towards CM and this net effect was mostly reversed by an FPR1 antagonist. Using an established mouse model of injury-dependent lung infection, we then showed simple instillation of exogenous unstimulated human neutrophils into the airway resulted in bacterial clearance from the lung. Conclusion Injury-derived mtFPs suppress global PMN localization into complex chemotactic environments like infected alveoli. Transplantation of naive exogenous human neutrophils into the airway circumvents that pathologic process and prevents development of post-traumatic pneumonia without injury noted to the recipients. |
| Databáze: | OpenAIRE |
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