G-CSF-induced emergency granulopoiesis modulates neutrophil effector function in mice 3345

Abstract Description Neutrophils function as first responders of the immune system by deploying cytotoxic armaments and orchestrating local inflammation. Their functionality is programmed during daily production in the bone marrow through granulopoiesis. During severe inflammation, increase in neutrophil demand is met through activation of emergency granulopoiesis. The effect of emergency granulopoiesis on neutrophil functionality remains cryptic. In the present study, we assessed neutrophil function in mice injected with G-CSF (100 µg/kg/d for 3 days) to activate emergency granulopoiesis. We found that emergency granulopoiesis neutrophils exhibit impaired ROS production (n = 6, P < 0.01) and NETosis (n = 5, P < 0.01), but increase in neutrophil elastase secretion (n = 9, P < 0.0001) and LPS-induced Tnfa, Il1b, Il1a, Il12a, and Ccl2 expression (n = 13, P < 0.01). To test the impact of emergency granulopoiesis neutrophils on the inflammatory response in vivo, we pre-treated mice with G-CSF and challenged them with zymosan to induce peritonitis. At 4 h post-zymosan injection, peritoneal neutrophils from G-CSF treated mice exhibit increased expression of Ccl2 (n = 3, P < 0.05). Subsequently, we observe enhanced peritoneal macrophage accumulation at 48 h post-zymosan administration in G-CSF treated mice (n = 5, P < 0.05). These data indicate that emergency granulopoiesis programs neutrophils with an enhanced immunomodulatory function that orchestrates subsequent macrophage response in local tissue inflammation. Funding Sources Supported by NIH F31HL174069; AHA 24PRE1243117; NIH T32AI132146; NIH R01HL141191; NIH P01HL078825; Jewish Heritage Fund - Research Enhancement Award. Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)