Neutrophil cell surface receptors and their intracellular signal transduction pathways

Article ID	Journal	Published Year	Pages	File Type
5833133	International Immunopharmacology	2013	13 Pages	PDF

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 Ca2Â + 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

NF-κB PI3K NOD Jnk RAP RAC MIP BCR MYD88 ASC TCr ICAM-1 TGFβ ERK MCL FGR SRC C3G FCR ABL IκB ERM IP3 GPCR PLC TLR PKC GPi IKK DISC FADD GM-CSF PAK PKB LFA-1 DAP12 GRK MAP kinase kinase LTB4 SOCS VCAM-1 ZAP-70 SHP-1 NLRP3 IRF VLA-4 Tyk2 MDA5 ADAP RIG SH2 fMLP TRAF TRADD ITAM PIP3 VASP PSGL-1 FcRγ RIP3 GPCR kinase OSCAR ezrin-radixin-moesin SLP-76 CLEC Epac1 TNF TGFβ-activated kinase 1 Ras-related protein myeloid differentiation protein 88 P-selectin glycoprotein ligand Nod-like receptor family, pyrin domain containing 3 TAK CalDAG-GEFI SH2 domain-containing leukocyte protein of 76 kDa Janus kinase c-Jun N-terminal kinase cIAP Fc-receptor GTPase Activating Protein IκB kinase MKK ROS STAT inflammation interferon IFN interleukin cellular Inhibitor of Apoptosis Cho Pir Syk Transforming growth factor β Toll-like receptor diacyl-glycerol Rank DAG suppressor of cytokine signaling Chinese hamster ovary cells Signaling GAP spleen tyrosine kinase IFN regulatory factor Platelet activating factor TNF receptor-associated factor IRAK granulocyte colony-stimulating factor G-CSF tumor necrosis factor nuclear factor κB phosphatidylinositol-3-phosphate phospholipase C Vasodilator-stimulated phosphoprotein caspase activation and recruitment domain TRAIL TREM LAD Leukotriene B4 C-type lectin TNF-related apoptosis-inducing ligand Signal transducer and activator of transcription inhibitor of NF-κB immunoreceptor tyrosine-based activation motif Intercellular adhesion molecule 1 Vascular cell adhesion molecule 1 Mac-1 Neutrophils PAF Hck RAS-related C3 botulinum toxin substrate macrophage inflammatory protein Melanoma Differentiation-Associated protein 5 Fas-associated protein with death domain apoptosis-associated speck-like protein containing a CARD protein kinase B Protein kinase C mitogen-activated protein kinase death-inducing signaling complex JAK retinoic acid-inducible gene CARD Leukocyte adhesion deficiency MAP kinase extracellular signal-regulated kinase hematopoietic cell kinase p21-activated kinase IL-1 receptor-associated kinase Kinases Reactive oxygen species glycosylphosphatidylinositol anchor triggering receptor expressed on myeloid cells B-cell receptor T-cell receptor Receptors osteoclast-associated receptor receptor activator of NF-κB G protein-coupled receptor