Cell and Tissue Research

, Volume 371, Issue 3, pp 455–471 | Cite as

Armed for destruction: formation, function and trafficking of neutrophil granules

Review

Abstract

Neutrophils respond nearly instantly to infection, rapidly deploying a potent enzymatic and chemical arsenal immediately upon entering an infected site. This capacity for rapid and potent responses is endowed by stores of antimicrobial proteins contained in readily mobilizable granules. These granules contain the proteins necessary to mediate the recruitment, chemotaxis, antimicrobial function and NET formation of neutrophils. Four granule types exist, and are sequentially deployed as neutrophils enter infected sites. Secretory vesicles are released first, enabling recruitment of neutrophils out of the blood. Next, specific and gelatinase granules are released to enable neutrophil migration and begin the formation of an antimicrobial environment. Finally, azurophilic granules release potent antimicrobial proteins at the site of infection and into phagosomes. The step-wise mobilization of these granules is regulated by calcium signaling, while specific trafficking regulators and membrane fusion complexes ensure the delivery of granules to the correct subcellular site. In this review, we describe neutrophil granules from their formation through to their deployment at the site of infection, focusing on recent developments in our understanding of the signaling pathways and vesicular trafficking mechanisms which mediate neutrophil degranulation.

Keywords

Neutrophil Degranulation Granulopoiesis Calcium GTPase Vesicular traffic 

Abbreviations

AP

Adaptor protein

CHS

Chédiak–Higashi syndrome

CR3

Complement receptor 3

DAG

Diacylglycerol

DOCK2

Dedicator of cytokinesis protein 2

ER

Endoplasmic reticulum

FcR

Fc receptor

fMLF

N-formylmethionyl-leucyl-phenylalanine

GAP

GTPase activating protein

GEF

Guanine exchange factor

GPCR

G protein-coupled receptor

IP3

Inositol-3-phosphate

ITAM

Immunoreceptor tyrosine-based activation motif

MPO

Myeloperoxidase

NET

Neutrophil extracellular trap

PA

Phosphatidic acid

PI3K

Phosphatidyleinositiol-3-kinase

SFK

Src-family kinase

SGD

Specific granule deficiency

SNAP

Synaptosomal-associated protein

SOC

Store-operated channel

SV

Secretory vesicle

VAMP

Vesicle-associated membrane protein.

Notes

Acknowledgements

The work in B.H.’s laboratory is supported by an operating grant from the Canadian Institutes for Health Research (MOP-123419), discovery grant #418194 from the Natural Sciences and Engineering Council of Canada, and an Ontario Ministry of Research and Innovation Early Researcher Award. C.Y. is a Vanier Scholar and holds a Canadian Institutes for Health Research MD/PhD Studentship.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Department of Microbiology and Immunology and the Center for Human ImmunologyThe University of Western OntarioLondonCanada

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