Neutrophil trogocytosis during their trans-endothelial migration: role of extracellular CIRP

BACKGROUND: Neutrophils are the most abundant innate immune cells in the circulating blood, and they act as the first responder against bacterial and fungal infection. However, accumulation of activated neutrophils can cause severe inflammation and tissue damage. Recently, neutrophil trogocytosis or membrane transfer with neighboring cells was reported to modulate immune responses. Extracellular cold-inducible RNA binding protein (eCIRP) is a newly identified damage-associated molecular pattern (DAMP). eCIRP can activate neutrophils to be more pro-inflammatory. This study aimed to identify the role of eCIRP in neutrophil trogocytosis during their trans-endothelial migration. METHODS: A trans-endothelial migration (TEM) assay using bone marrow neutrophils and mouse primary lung vascular endothelial cells was conducted using transwell chambers and neutrophil trogocytosis was assessed in vitro. In an in vivo mouse model of acute lung injury, neutrophil trogocytosis was assessed from bronchoalveolar lavage fluid. RESULTS: In TEM assay, the trogocytosis of neutrophils occurred during trans-endothelial migration and eCIRP significantly increased the percentage of these neutrophils. The trogocytosed neutrophils acquired the endothelial membrane containing junctional adhesion molecule-C (JAM-C) and VE-cadherin, and these membrane patches were polarized by Mac-1 binding. Furthermore, eCIRP-induced JAM-C positive trogocytosed neutrophils are more pro-inflammatory than the JAM-C negative counterpart. JAM-C positive trogocytosed neutrophils were also observed in the bronchoalveolar lavage fluid of a mouse model of acute lung injury. CONCLUSION: These data suggest that during the paracellular trans-endothelial migration of neutrophils in response to inflammation, eCIRP induces trogocytosis of neutrophils, and the trogocytosed neutrophils exhibit an exaggerated pro-inflammatory phenotype promoting acute lung injury. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s10020-022-00515-3.