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PMID: 23994464 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Neutrophil cell surface receptors and their intracellular signal transduction pathways.

International immunopharmacology ·Vol. 17 ·No. 3 ·2013-11-00 ·Pages 638-50

Futosi K, Fodor S, Mócsai A

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 Ca(2+) 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.

Keywords
ADAP Abelson leukemia proto-oncogene Abl Asc B-cell receptor BCR C-type lectin C3G CALDAG-GEFI CARD CEACAM3 CHO CLEC Chinese hamster ovary cells Crk SH3 domain-binding guanine nucleotide exchange factor (RapGEF1) DAG DAP12 DISC DNAX activating protein 12 E-selectin ligand 1 ERK ERM ESL-1 Epac1 FADD Fas-associated protein with death domain Fc-receptor Fc-receptor γ-chain FcR FcRγ Fgr G protein-coupled receptor G-CSF GAP GM-CSF GPCR GPCR kinase GPI GRK GTPase activating protein Gardner–Rasheed feline sarcoma proto-oncogene Hck ICAM-1 IFN IFN regulatory factor IKK IL IL-1 receptor-associated kinase IP(3) IRAK IRF ITAM Inflammation IκB IκB kinase JAK JNK Janus kinase Kinases LAD LFA-1 LTB(4) LTβ MAP kinase MAP kinase kinase MAP kinase-associated protein kinase MAPKAP-kinase MDA5 MDL-1 MIP MKK Mac-1 Mcl MyD88 NF-κB NLRP3 NOD NOD-like receptor family pyrin domain containing 3 Neutrophils OSCAR P-selectin glycoprotein ligand PAF PAK PI3K PIP(3) PIR PKB PKC PLC PSGL-1 RANK RIG RIP3 ROS Rac Rap Ras-related C3 botulinum toxin substrate Ras-related protein Receptors Rous sarcoma virus proto-oncogene SAP130 SH2 SH2 domain-containing leukocyte protein of 76kDa SH2 domain-containing protein tyrosine phosphatase 1 SHP-1 SLP-76 SOCS STAT Signaling Sin3A-associated protein of 130kDa Src Src-homology 2 domain Syk T-cell receptor TAK TCR TGFβ TGFβ-activated kinase 1 TLR TNF TNF receptor-associated factor TNF-related apoptosis-inducing ligand TNFR1-associated death domain protein TRADD TRAF TRAIL TREM Toll-like receptor Tyk2 VASP VCAM-1 VLA-4 ZAP-70 adhesion and degranulation promoting adapter protein (Fyb SLAP-130) apoptosis-associated speck-like protein containing a CARD c-Jun N-terminal kinase cIAP calcium and DAG-regulated guanine nucleotide exchange factor I carcinoembryonic antigen-related cell adhesion molecule 3 (CD66b) caspase activation and recruitment domain cellular inhibitor of apoptosis death-inducing signaling complex diacyl-glycerol exchange protein activated by cyclic AMP 1 extracellular signal-regulated kinase ezrin-radixin-moesin fMLP formly-Met-Leu-Phe glycosylphosphatidylinositol anchor granulocyte colony-stimulating factor granulocyte/monocyte colony-stimulating factor hematopoietic cell kinase immunoreceptor tyrosine-based activation motif inhibitor of NF-κB inositol-tris-phosphate intercellular adhesion molecule 1 interferon interleukin leukocyte adhesion deficiency leukotriene B(4) lymphocyte function-associated receptor 1 (α(L)β(2) integrin) lymphotoxin β macrophage C-type lectin macrophage antigen 1 (α(M)β(2) integrin) macrophage inflammatory protein melanoma differentiation-associated protein 5 mitogen-activated protein kinase myeloid DAP12-associating lectin 1 myeloid differentiation protein 88 nuclear factor κB nucleotide-binding oligomerization domain containing protein osteoclast-associated receptor p21-activated kinase paired immunoglobulin-like receptor phoshoinositide-3-kinase phosphatidylinositol-3-phosphate phospholipase C platelet activating factor protein kinase B protein kinase C reactive oxygen species receptor activator of NF-κB receptor-interacting serine-threonine protein kinase 3 retinoic acid-inducible gene signal transducer and activator of transcription spleen tyrosine kinase suppressor of cytokine signaling transforming growth factor β triggering receptor expressed on myeloid cells tumor necrosis factor tyrosine protein kinase 2 vascular cell adhesion molecule 1 vasodilator-stimulated phosphoprotein very late antigen 4 (α(4)β(1) integrin) ζ-chain-associated protein of 70kDa
MeSH Terms
Animals Humans Neutrophils/immunology Proto-Oncogene Mas Receptors, Cell Surface/immunology Selectins/immunology Signal Transduction/immunology
Chemicals
MAS1 protein, human Proto-Oncogene Mas Receptors, Cell Surface Selectins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Futosi Krisztina
Department of Physiology, Semmelweis University School of Medicine, 1094 Budapest, Hungary.
Fodor Szabina
Mócsai Attila
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Article Info
Journal
International immunopharmacology
Abbr.
Int Immunopharmacol
ISSN
1878-1705
DOI
10.1016/j.intimp.2013.06.034
Published
2013-11-00
Epub
2013-00-30
Pages
638-50
Language
English
Region
Netherlands
NLM ID
100965259
PMCID
PMC3827506
Subset
IM
Grants
Wellcome Trust · United Kingdom
European Research Council · 206283 · International
Wellcome Trust · 087782 · United Kingdom
External Links
PubMed source DOI: 10.1016/j.intimp.2013.06.034 PMC Full Text View journal details
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