Burn injury impairs neutrophil chemotaxis through increased ceramide
- Infection is a common and often deadly complication after burn injury. A major underlying factor is burn-induced immune dysfunction, particularly with respect to neutrophils as the primary responders to infection. Temporally after murine scald injury, we demonstrate impaired bone marrow neutrophil chemotaxis toward CXCL1 ex vivo. Additionally, we observed a reduced recruitment of neutrophils to the peritoneal after elicitation 7 days after injury. We demonstrate that neutrophil ceramide levels increase after burn injury, and this is associated with decreased expression of CXCR2 and blunted chemotaxis. A major signaling event upon CXCR2 activation is Akt phosphorylation and this was reduced when ceramide was elevated. In contrast, PTEN levels were elevated and PTEN-inhibition elevated phospho-Akt levels and mitigated the burn-induced neutrophil chemotaxis defect. Altogether, this study identifies a newly described pathway of ceramide-mediated suppression of neutrophil chemotaxis after burn injury and introduces potential targets toInfection is a common and often deadly complication after burn injury. A major underlying factor is burn-induced immune dysfunction, particularly with respect to neutrophils as the primary responders to infection. Temporally after murine scald injury, we demonstrate impaired bone marrow neutrophil chemotaxis toward CXCL1 ex vivo. Additionally, we observed a reduced recruitment of neutrophils to the peritoneal after elicitation 7 days after injury. We demonstrate that neutrophil ceramide levels increase after burn injury, and this is associated with decreased expression of CXCR2 and blunted chemotaxis. A major signaling event upon CXCR2 activation is Akt phosphorylation and this was reduced when ceramide was elevated. In contrast, PTEN levels were elevated and PTEN-inhibition elevated phospho-Akt levels and mitigated the burn-induced neutrophil chemotaxis defect. Altogether, this study identifies a newly described pathway of ceramide-mediated suppression of neutrophil chemotaxis after burn injury and introduces potential targets to mitigate this defect and reduce infection-related morbidity and mortality after burn.…
Author details: | Nadine Beckmann, Fabian SchumacherORCiDGND, Burkhard KleuserORCiDGND, Erich GulbinsORCiDGND, Vanessa Nomellini, Charles C. CaldwellORCiD |
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DOI: | https://doi.org/10.1097/SHK.0000000000001693 |
ISSN: | 1073-2322 |
ISSN: | 1540-0514 |
Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/33273368 |
Title of parent work (English): | Shock : injury, inflammation, and sepsis, laboratory and clinical approaches |
Publisher: | Lippincott Williams & Wilkins |
Place of publishing: | Hagerstown, Md. |
Publication type: | Article |
Language: | English |
Date of first publication: | 2021/12/01 |
Publication year: | 2021 |
Release date: | 2024/05/27 |
Tag: | Acid sphingomyelinase; Akt; CXCR2; PTEN; burn injury; ceramide; dysfunction; immune; neutrophil chemotaxis |
Volume: | 56 |
Issue: | 1 |
Number of pages: | 8 |
First page: | 125 |
Last Page: | 132 |
Funding institution: | National Institute of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [K08-GM-13128401/VN]; Shriner's Hospital for Children grant [85129-CIN/CCC] |
Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft |
DDC classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Peer review: | Referiert |