Regulatory Mechanisms in Neutrophil Degranulation

  • Lindsey C. Felix
  • Sarah Almas
  • Paige LacyEmail author


Bone marrow-derived circulating neutrophils of the innate immune system extravasate through blood vessel walls to sites of infection and injury where they orchestrate a myriad of protective and destructive host responses during acute inflammation. Although neutrophils comprise the first line of defense against exogenous and endogenous insults, these abundantly produced white blood cells can damage tissues and consequently increase the severity of inflammatory diseases. Neutrophils undergo receptor-mediated respiratory burst and release inflammatory mediators by degranulation of membrane-bound secretory granules after migrating from the bloodstream in response to chemotactic signals generated at inflammatory foci. Many studies point to degranulation as the chief causative process involved in inflammatory disorders, but the underlying mechanisms remain poorly understood. We discuss the complex interplay of distal, intracellular pathways involving numerous signaling proteins that are implicated in the exocytosis of granular contents. This review summarizes current knowledge of neutrophil biology and highlights mechanisms that regulate degranulation.


Actin cytoskeleton Exocytosis Granules Granulocytes Guanosine triphosphatases Kinases Myeloperoxidase Phosphoinositides Reactive oxygen species SNAREs 



V-ATPase subunit


Adenosine triphosphate


Adenosine triphosphatase


Botulinum neurotoxin


Endoplasmic reticulum


Extracellular signal-regulated kinase




Guanosine diphosphate


Guanine nucleotide exchange factor


G protein-coupled receptor


Guanosine triphosphate


Guanosine triphosphatase


Guanosine 5′-O-(γ-thio) triphosphate






Mitogen-activated protein


Myristoylated alanine-rich C kinase substrate


Matrix metalloprotease




Nicotinamide adenine dinucleotide phosphate


Neutrophil extracellular trap


Neutrophil exocytosis inhibitors


N-ethylmaleimide-sensitive factor


Phosphatidylinositol 3-kinase


FYVE domain-containing phosphatidylinositol 3-phosphate 5-kinase


Phosphatidylinositol 4,5-bisphosphate


Phorbol 12-myristate 13-acetate


Protein tyrosine phosphatase MEG2


SNARE expressing a key glutamine residue in the SNARE-binding domain; also known as t-SNARE in exocytosis; members include syntaxins, SNAP-23, and SNAP-25


ras-related C3 botulinum toxin substrate


Reactive oxygen species


SNARE expressing a key arginine residue in the SNARE-binding domain; also known as v-SNARE in exocytosis; members include VAMPs


src family of non-receptor tyrosine kinases


N-ethylmaleimide-sensitive factor attachment protein or synaptosomal-associated protein


N-ethylmaleimide-sensitive factor attachment protein receptor


Secretory vesicle N-ethylmaleimide-sensitive factor attachment protein receptor


Tetanus neurotoxin


Toll-like receptor


Vesicle-associated membrane protein


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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Alberta Respiratory Centre (ARC) Research, Department of MedicineUniversity of AlbertaEdmontonCanada

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