[HTML][HTML] Mechanism of pulmonary immunosuppression: extrapulmonary burn injury suppresses bacterial endotoxin–induced pulmonary neutrophil recruitment and …

M Sakuma, MAS Khan, S Yasuhara, JA Martyn… - The FASEB …, 2019 - ncbi.nlm.nih.gov
M Sakuma, MAS Khan, S Yasuhara, JA Martyn, N Palaniyar
The FASEB Journal, 2019ncbi.nlm.nih.gov
Pulmonary immunosuppression often occurs after burn injury (BI). However, the reasons for
BI-induced pulmonary immunosuppression are not clearly understood. Neutrophil
recruitment and neutrophil extracellular trap (NET) formation (NETosis) are important
components of a robust pulmonary immune response, and we hypothesized that pulmonary
inflammation and NETosis are defective after BI. To test this hypothesis, we established a
mouse model with intranasal LPS instillation in the presence or absence of BI (15% of body …
Abstract
Pulmonary immunosuppression often occurs after burn injury (BI). However, the reasons for BI-induced pulmonary immunosuppression are not clearly understood. Neutrophil recruitment and neutrophil extracellular trap (NET) formation (NETosis) are important components of a robust pulmonary immune response, and we hypothesized that pulmonary inflammation and NETosis are defective after BI. To test this hypothesis, we established a mouse model with intranasal LPS instillation in the presence or absence of BI (15% of body surface burn) and determined the degree of immune cell infiltration, NETosis, and the cytokine levels in the airways and blood on d 2. Presence of LPS recruited monocytes and large numbers of neutrophils to the airways and induced NETosis (citrullinated histone H3, DNA, myeloperoxidase). By contrast, BI significantly reduced LPS-mediated leukocyte recruitment and NETosis. This BI-induced immunosuppression is attributable to the reduction of chemokine (CC motif) ligand (CCL) 2 (monocyte chemoattractant protein 1) and CCL3 (macrophage inflammatory protein 1α). BI also suppressed LPS-induced increase in IL-17A, IL-17C, and IL-17E/IL-25 levels in the airways. Therefore, BI-mediated reduction in leukocyte recruitment and NETosis in the lungs are attributable to these cytokines. Regulating the levels of some of these key cytokines represents a potential therapeutic option for mitigating BI-mediated pulmonary immunosuppression.—Sakuma, M., Khan, MAS, Yasuhara, S., Martyn, JA, Palaniyar, N. Mechanism of pulmonary immunosuppression: extrapulmonary burn injury suppresses bacterial endotoxin–induced pulmonary neutrophil recruitment and neutrophil extracellular trap (NET) formation.
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