Neutrophil in Reverse Migration: Role in Sepsis

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.

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“…It is downregulated by iron-containing 2-oxoglutarate-dependent enzymes (abovementioned hydroxylases) having ascorbate as a cofactor [22]. As was mentioned by Ji and Fan [28], some studies revealed negative regulation of PMN rM with the suppressing role of HIF-1α, noted in zebrafish. Elks et al [33] with use of indirect HIF inhibitor, dimethyloxaloyglycine (DMOG) revealed that activated HIF-1α delays resolution of inflammation and it is a consequence of reduced neutrophil apoptosis and increased retention of these cells at the site of injury.…”

“…With the development of imaging technology, it has been found that the recruited polymorphonuclear leukocytes (PMNs) could migrate back to the circulation and it is a new way of PMN clearance in inflammatory or injury site. This process without undergoing apoptosis has been called as “PMN reverse migration (rM)” [ 28 ]. In 2004, Sharma et al [ 29 ] showed that after treatment of PMNs with E. coli or arachidonic acid, AA or DHA did not influence the phagocytosis of PMNs but improved ROS generation and apoptosis.…”

Neutrophil Migratory Patterns: Implications for Cardiovascular Disease

“…CXCL8 functions as a chemoattractant at lower concentrations, at higher concentrations, though, it acts as chemorepellent ( Tharp et al, 2006 ). In addition to these, other mechanisms have been proposed for reverse migration ( Elks et al, 2011 ; Nourshargh et al, 2016 ; Ji and Fan, 2021 ). Although an interesting and promising pathway, many questions remain unanswered in the process of reverse migration and more research must be conducted before we fully uncover the mechanistic details behind this orchestrated movement of neutrophils in the context of inflammation.…”

Neutrophils at the crossroads of acute viral infections and severity

“…The ICAM1 high /CXCR1 low are long-lived with increased ROS levels and increased propensity to produce NETs ( Cerutti et al, 2013 ; Villanueva et al, 2011 ). Although the role of these rTM neutrophils can be both protective and tissue-damaging, but current studies suggest their detrimental roles in case of sepsis ( Ji and Fan, 2021 ), trauma, ischemia-reperfusion, and other chronic inflammatory diseases ( Hirano et al, 2016 ). Further studies need to be done to identify these rTM neutrophils in case of severe viral infections.…”