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Regulatory Mechanisms in Neutrophil Degranulation

  • Lindsey C. Felix
  • Sarah Almas
  • Paige Lacy
Chapter

Abstract

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.

Keywords

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

Abbreviations

a2V

V-ATPase subunit

ATP

Adenosine triphosphate

ATPase

Adenosine triphosphatase

BoNT

Botulinum neurotoxin

ER

Endoplasmic reticulum

ERK

Extracellular signal-regulated kinase

fMLP

N-formyl-methionyl-leucyl-phenylalanine

GDP

Guanosine diphosphate

GEF

Guanine nucleotide exchange factor

GPCR

G protein-coupled receptor

GTP

Guanosine triphosphate

GTPase

Guanosine triphosphatase

GTPγS

Guanosine 5′-O-(γ-thio) triphosphate

IL-8

Interleukin-8

LTF

Lactoferrin

MAP

Mitogen-activated protein

MARCKS

Myristoylated alanine-rich C kinase substrate

MMP

Matrix metalloprotease

MPO

Myeloperoxidase

NADPH

Nicotinamide adenine dinucleotide phosphate

NET

Neutrophil extracellular trap

Nexinhibs

Neutrophil exocytosis inhibitors

NSF

N-ethylmaleimide-sensitive factor

PI3K

Phosphatidylinositol 3-kinase

PIKfyve

FYVE domain-containing phosphatidylinositol 3-phosphate 5-kinase

PIP2

Phosphatidylinositol 4,5-bisphosphate

PMA

Phorbol 12-myristate 13-acetate

PTP-MEG2

Protein tyrosine phosphatase MEG2

Q-SNARE

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

Rac

ras-related C3 botulinum toxin substrate

ROS

Reactive oxygen species

R-SNARE

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

SFKs

src family of non-receptor tyrosine kinases

SNAP

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

SNARE

N-ethylmaleimide-sensitive factor attachment protein receptor

SV

Secretory vesicle N-ethylmaleimide-sensitive factor attachment protein receptor

TeNT

Tetanus neurotoxin

TLR

Toll-like receptor

VAMP

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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