Neutrophil cell surface receptors and their intracellular signal transduction pathways

https://doi.org/10.1016/j.intimp.2013.06.034Get rights and content
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Highlights

  • Neutrophils are crucial players in innate and adaptive immunity.

  • Neutrophils also participate in autoimmune and inflammatory diseases.

  • Various neutrophil receptors recognize pathogens and the inflammatory environment.

  • The various cell surface receptors trigger diverse intracellular signaling.

  • Neutrophil receptors and signaling are potential targets in inflammatory diseases.

Abstract

Neutrophils play a critical role in the host defense against bacterial and fungal infections, but their inappropriate activation also contributes to tissue damage during autoimmune and inflammatory diseases. Neutrophils express a large number of cell surface receptors for the recognition of pathogen invasion and the inflammatory environment. Those include G-protein-coupled chemokine and chemoattractant receptors, Fc-receptors, adhesion receptors such as selectins/selectin ligands and integrins, various cytokine receptors, as well as innate immune receptors such as Toll-like receptors and C-type lectins. The various cell surface receptors trigger very diverse signal transduction pathways including activation of heterotrimeric and monomeric G-proteins, receptor-induced and store-operated Ca2 + signals, protein and lipid kinases, adapter proteins and cytoskeletal rearrangement. Here we provide an overview of the receptors involved in neutrophil activation and the intracellular signal transduction processes they trigger. This knowledge is crucial for understanding how neutrophils participate in antimicrobial host defense and inflammatory tissue damage and may also point to possible future targets of the pharmacological therapy of neutrophil-mediated autoimmune or inflammatory diseases.

Abbreviations

Abl
Abelson leukemia proto-oncogene
ADAP
adhesion and degranulation promoting adapter protein (Fyb, SLAP-130)
Asc
apoptosis-associated speck-like protein containing a CARD
BCR
B-cell receptor
C3G
Crk SH3 domain-binding guanine nucleotide exchange factor (RapGEF1)
CALDAG-GEFI
calcium and DAG-regulated guanine nucleotide exchange factor I
CARD
caspase activation and recruitment domain
CEACAM3
carcinoembryonic antigen-related cell adhesion molecule 3 (CD66b)
CHO
Chinese hamster ovary cells
cIAP
cellular inhibitor of apoptosis
CLEC
C-type lectin
DAG
diacyl-glycerol
DAP12
DNAX activating protein 12
DISC
death-inducing signaling complex
Epac1
exchange protein activated by cyclic AMP 1
ERK
extracellular signal-regulated kinase
ERM
ezrin-radixin-moesin
ESL-1
E-selectin ligand 1
FADD
Fas-associated protein with death domain
FcR
Fc-receptor
FcRγ
Fc-receptor γ-chain
Fgr
Gardner–Rasheed feline sarcoma proto-oncogene
fMLP
formly-Met-Leu-Phe
GAP
GTPase activating protein
G-CSF
granulocyte colony-stimulating factor
GM-CSF
granulocyte/monocyte colony-stimulating factor
GPCR
G protein-coupled receptor
GPI
glycosylphosphatidylinositol anchor
GRK
GPCR kinase
Hck
hematopoietic cell kinase
ICAM-1
intercellular adhesion molecule 1
IFN
interferon
IKK
IκB kinase
IL
interleukin
IP3
inositol-tris-phosphate
IRAK
IL-1 receptor-associated kinase
IRF
IFN regulatory factor
ITAM
immunoreceptor tyrosine-based activation motif
IκB
inhibitor of NF-κB
JAK
Janus kinase
JNK
c-Jun N-terminal kinase
LAD
leukocyte adhesion deficiency
LFA-1
lymphocyte function-associated receptor 1 (αLβ2 integrin)
LTβ
lymphotoxin β
LTB4
leukotriene B4
Mac-1
macrophage antigen 1 (αMβ2 integrin)
MAP kinase
mitogen-activated protein kinase
MAPKAP-kinase
MAP kinase-associated protein kinase
Mcl
macrophage C-type lectin
MDA5
melanoma differentiation-associated protein 5
MDL-1
myeloid DAP12-associating lectin 1
MIP
macrophage inflammatory protein
MKK
MAP kinase kinase
MyD88
myeloid differentiation protein 88
NF-κB
nuclear factor κB
NLRP3
NOD-like receptor family, pyrin domain containing 3
NOD
nucleotide-binding oligomerization domain containing protein
OSCAR
osteoclast-associated receptor
PAF
platelet activating factor
PAK
p21-activated kinase
PI3K
phoshoinositide-3-kinase
PIP3
phosphatidylinositol-3-phosphate
PIR
paired immunoglobulin-like receptor
PKB
protein kinase B
PKC
protein kinase C
PLC
phospholipase C
PSGL-1
P-selectin glycoprotein ligand
Rac
Ras-related C3 botulinum toxin substrate
RANK
receptor activator of NF-κB
Rap
Ras-related protein
RIG
retinoic acid-inducible gene
RIP3
receptor-interacting serine-threonine protein kinase 3
ROS
reactive oxygen species
SAP130
Sin3A-associated protein of 130 kDa
SH2
Src-homology 2 domain
SHP-1
SH2 domain-containing protein tyrosine phosphatase 1
SLP-76
SH2 domain-containing leukocyte protein of 76 kDa
SOCS
suppressor of cytokine signaling
Src
Rous sarcoma virus proto-oncogene
STAT
signal transducer and activator of transcription
Syk
spleen tyrosine kinase
TAK
TGFβ-activated kinase 1
TCR
T-cell receptor
TGFβ
transforming growth factor β
TLR
Toll-like receptor
TNF
tumor necrosis factor
TRADD
TNFR1-associated death domain protein
TRAF
TNF receptor-associated factor
TRAIL
TNF-related apoptosis-inducing ligand
TREM
triggering receptor expressed on myeloid cells
Tyk2
tyrosine protein kinase 2
VASP
vasodilator-stimulated phosphoprotein
VCAM-1
vascular cell adhesion molecule 1
VLA-4
very late antigen 4 (α4β1 integrin)
ZAP-70
ζ-chain-associated protein of 70 kDa

Keywords

Neutrophils
Signaling
Receptors
Kinases
Inflammation

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