Delayed CCL23 response is associated with poor outcomes after cardiac arrest
Document Type
Article
Publication Date
4-2024
Institution/Department
MaineHealth Insitute for Research, Center for Molecular Medicine
Journal Title
Cytokine
MeSH Headings
Humans; Mice; Animals; Heart Arrest (complications); Chemokines; Chemokines, CC
Abstract
Chemokines, a family of chemotactic cytokines, mediate leukocyte migration to and entrance into inflamed tissue, contributing to the intensity of local inflammation. We performed an analysis of chemokine and immune cell responses to cardiac arrest (CA). Forty-two patients resuscitated from cardiac arrest were analyzed, and twenty-two patients who underwent coronary artery bypass grafting (CABG) surgery were enrolled. Quantitative antibody array, chemokines, and endotoxin quantification were performed using the patients blood. Analysis of CCL23 production in neutrophils obtained from CA patients and injected into immunodeficient mice after CA and cardiopulmonary resuscitation (CPR) were done using flow cytometry. The levels of CCL2, CCL4, and CCL23 are increased in CA patients. Temporal dynamics were different for each chemokine, with early increases in CCL2 and CCL4, followed by a delayed elevation in CCL23 at forty-eight hours after CA. A high level of CCL23 was associated with an increased number of neutrophils, neuron-specific enolase (NSE), worse cerebral performance category (CPC) score, and higher mortality. To investigate the role of neutrophil activation locally in injured brain tissue, we used a mouse model of CA/CPR. CCL23 production was increased in human neutrophils that infiltrated mouse brains compared to those in the peripheral circulation. It is known that an early intense inflammatory response (within hours) is associated with poor outcomes after CA. Our data indicate that late activation of neutrophils in brain tissue may also promote ongoing injury via the production of CCL23 and impair recovery after cardiac arrest.
First Page
156536
Recommended Citation
deKay, Joanne T.; Chepurko, Elena; Chepurko, Vadim; Knudsen, Lacey; Lord, Christine; Searight, Meghan; Tsibulnikov, Sergey; Robich, Michael P.; Sawyer, Douglas; and May, Teresa, "Delayed CCL23 response is associated with poor outcomes after cardiac arrest" (2024). Maine Medical Center. 3630.
https://knowledgeconnection.mainehealth.org/mmc/3630
