'A distinct neutrophil population invades the central nervous system during pancreatic cancer'
| Autor: | Shannon K. McWeeney, Mason A. Norgard, Daniel L. Marks, Xinxia Zhu, Jacob Raber, Kevin G. Burfeind, Katherine A. Michaelis, Sophia Jeng, Brennan Olson, Eileen Ruth S. Torres, Peter R. Levasseur, Esha M. Patel |
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| Rok vydání: | 2019 |
| Předmět: |
0303 health sciences
education.field_of_study business.industry Population Central nervous system Inflammation Anorexia medicine.disease 3. Good health 03 medical and health sciences 0302 clinical medicine Neuroimmunology medicine.anatomical_structure Pancreatic cancer Knockout mouse medicine Cancer research medicine.symptom education business 030217 neurology & neurosurgery Neuroinflammation 030304 developmental biology |
| Popis: | Weight loss, fatigue, and cognitive dysfunction are common symptoms in cancer patients that occur prior to initiation of cancer therapy. Inflammation in the brain is a driver of these symptoms, yet cellular sources of neuroinflammation during malignancy are unknown. In a mouse model of pancreatic ductal adenocarcinoma (PDAC), we observed early and robust myeloid cell infiltration into the brain. Infiltrating immune cells were predominately neutrophils, which accumulated at a unique central nervous system entry portal called the velum interpositum, where they expressed CCR2. CCR2 knockout mice had significantly decreased brain-infiltrating neutrophils as well as attenuated anorexia and muscle catabolism during PDAC, without any changes in neutrophils in other organs. Lastly, intracerebroventricular blockade of the purinergic receptor P2RX7 during PDAC abolished neutrophil recruitment to the brain and attenuated anorexia. Our data demonstrate a novel function for the CCR2/CCL2 axis in recruiting neutrophils to the brain, which drives anorexia and muscle catabolism. |
| Databáze: | OpenAIRE |
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