Filep JG, Ariel A. Neutrophil heterogeneity and fate in inflamed tissues: implications for the resolution of inflammation. Am J Physiol Cell Physiol 319: C510–C532, 2020. First published July 15, 2020; doi:10.1152/ajpcell.00181.2020.—Neutrophils are polymorphonuclear leukocytes that play a central role in host defense against infection and tissue injury. They are rapidly recruited to the inflamed site and execute a variety of functions to clear invading pathogens and damaged cells. However, many of their defense mechanisms are capable of inflicting collateral tissue damage. Neutrophil-driven inflammation is a unifying mechanism underlying many common diseases. Efficient removal of neutrophils from inflammatory loci is critical for timely resolution of inflammation and return to homeostasis. Accumulating evidence challenges the classical view that neutrophils represent a homogeneous population and that halting neutrophil influx is sufficient to explain their rapid decline within inflamed loci during the resolution of protective inflammation. Hence, understanding the mechanisms that govern neutrophil functions and their removal from the inflammatory locus is critical for minimizing damage to the surrounding tissue and for return to homeostasis. In this review, we briefly address recent advances in characterizing neutrophil phenotypic and functional heterogeneity and the molecular mechanisms that determine the fate of neutrophils within inflammatory loci and the outcome of the inflammatory response. We also discuss how these mechanisms may be harnessed as potential therapeutic targets to facilitate resolution of inflammation.
|Journal||American Journal of Physiology - Cell Physiology|
|State||Published - Sep 2020|
Bibliographical noteFunding Information:
This work was supported by Canadian Institutes of Health Research Grants MOP-97742 and MOP-102619 (to J.G.F.), Israel Science Foundation Grant No. 678/13, the Rosetrees Trust, and the Wolfson Family Charitable Trust (to A.A.).
© 2020 the American Physiological Society
- Cell death
- Neutrophil trafficking
- Specialized proresolving mediators
- Host-Derived Cellular Factors/metabolism
ASJC Scopus subject areas
- Cell Biology