Neutrophil in Reverse Migration: Role in Sepsis

Jingjing Ji, Jie Fan, Jingjing Ji, Jie Fan

Abstract

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. During the development and progression of sepsis, polymorphonuclear neutrophils (PMNs) are the most abundantly recruited innate immune cells at sites of infection, playing critical roles in the elimination of local infection and healing of the injury. PMN reverse migration (rM) describes the phenomenon in which PMNs migrate away from the inflammatory site back into the vasculature following the initial PMN infiltration. The functional role of PMN rM within inflammatory scenarios requires further exploration. Current evidence suggests that depending on the context, PMN rM can be both a protective response, by facilitating an efficient resolution to innate immune reaction, and also a tissue-damaging event. In this review, we provide an overview of current advancements in understanding the mechanism and roles of PMN rM in inflammation and sepsis. A comprehensive understanding of PMN rM may allow for the development of novel prophylactic and therapeutic strategies for sepsis.

Keywords: PMN; infection; inflammation; rerverse migration; sepsis.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Ji and Fan.

Figures

Figure 1
Figure 1
Mechanisms of PMN rM. 1. Breach of endothelium results in leakage of chemokine, i.e., CXCL1, from the inflammatory site into the vasculature, therefore driving PMN to reenter the circulation; 2. LTB4 induces PMN release of neutrophil elastase (NE), which in turn cleaves endothelial JAM-C and subsequent damage of endothelial junction and promotes PMN rM. The binding between PMN CD11b/CD18 and endothelial ICAM-1 retains the PMN on the surface of endothelial cells and secures the cleavage of JAM-C by NE; 3. Activation of HIF1α suppresses PMN rM; and 4. Many factors, including cold-inducible RNA-binding protein (CIRP), Lipoxin A4, PEG2, and cathepsin C, can promote PMN rM. The phenotype of reverse migrated PMN (rM-ed PMN) is ICAM1high CXCR1low.

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