Neutrophil in Reverse Migration: Role in Sepsis.

Jingjing Ji,Jie Fan

doi:10.3389/fimmu.2021.656039

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.

Highlights

Polymorphonuclear neutrophils (PMNs) are the first responders in the circulation, playing an important role in defending against invading pathogens [1]
The mechanism of sepsis remains to be fully elucidated, which results in poor therapeutic outcomes for septic patients
Despite advances in understanding PMN biology over the last several decades, there remains a significant gap in our knowledge regarding various PMN functions and behavior in sepsis

Summary

INTRODUCTION

Polymorphonuclear neutrophils (PMNs) are the first responders in the circulation, playing an important role in defending against invading pathogens [1]. With the development of imaging technology, it has been found that the recruited PMNs could migrate back to the circulation, which serves as a new way of PMN clearance in inflammatory or injury site [8, 9]. In 1997, Hughes et al using a rat glomerular capillary injury model and radiolabeling of PMN found that over 70% of PMNs that entered inflamed glomerular capillaries were able to return to the main circulation without undergoing apoptosis in the inflammatory site [8, 10]. In 2017, in vivo PMN rM in mice was visualized by Wang et al in a sterile thermal hepatic injury model, in which reverse migrated PMNs from the inflammatory site were imaged in the lungs and bone marrow [17]. The published data support the note that PMN rM is an important biological conservative phenomenon existing in from zebrafish to humans [11, 14, 17,18,19,20,21]

CURRENT KNOWLEDGE ON THE MECHANISMS OF PMN rM

BIOLOGICAL EFFECT OF PMN rM

PMN rM IN SEPSIS

SUMMARY