Fine-tuning neutrophil activation: Strategies and consequences.
In spite of their important role in host defense, neutrophils can also cause severe morbidity and mortality. Neutrophils have an extensive armory necessary to eradicate pathogens, but neutrophil infiltration and activation also induces major tissue injury associated with acute and chronic inflammatory disorders. Here, we review neutrophil anti-microbial functions and discuss their individual contribution to disease pathogenesis. Furthermore, we provide an overview of the anti-inflammatory drugs that can dampen neutrophil transmigration, elastase activity, and the production of reactive oxygen species which are already in clinical trials. The discovery of potential inhibitors of the release of neutrophil extracellular trap is still in its infancy. Here, we discuss small molecule inhibitors and inhibitory receptors that show promising results in reducing neutrophil extracellular trap formation in vitro and in vivo and discuss the advantages and drawbacks of inhibiting the release of neutrophil extracellular traps as a therapeutic treatment. Specific suppression of neutrophil extracellular trap formation, preferably while other antimicrobial functions are preserved, would be an ideal approach to treat neutrophilic inflammation, since it prevents acute as well as chronic neutrophil-associated pathology.
Laboratory of Translational Immunology, Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Maarten
M
van der Linden
Laboratory of Translational Immunology, Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: l.meyaard@umcutrecht.nl.
Linde
L
Meyaard
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D003602:Cytotoxicity, Immunologic; D004198:Disease Susceptibility; D065206:Extracellular Traps / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D018375:Neutrophil Activation / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species; D015398:Signal Transduction
D000893:Anti-Inflammatory Agents; D017382:Reactive Oxygen Species
Anti-inflammatory treatment; Collateral damage; Inhibitory receptors; Neutrophil; Neutrophil extracellular traps; Small molecule inhibitors