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Mechanisms of Degranulation in Neutrophils

By Paige Lacy

Abstract

Neutrophils are critical inflammatory cells that cause tissue damage in a range of diseases and disorders. Being bone marrow-derived white blood cells, they migrate from the bloodstream to sites of tissue inflammation in response to chemotactic signals and induce inflammation by undergoing receptor-mediated respiratory burst and degranulation. Degranulation from neutrophils has been implicated as a major causative factor in pulmonary disorders, including severe asphyxic episodes of asthma. However, the mechanisms that control neutrophil degranulation are not well understood. Recent observations indicate that granule release from neutrophils depends on activation of intracellular signalling pathways, including β-arrestins, the Rho guanosine triphosphatase Rac2, soluble NSF attachment protein (SNAP) receptors, the src family of tyrosine kinases, and the tyrosine phosphatase MEG2. Some of these observations suggest that degranulation from neutrophils is selective and depends on nonredundant signalling pathways. This review focuses on new findings from the literature on the mechanisms that control the release of granule-derived mediators from neutrophils

Topics: Review
Publisher: BioMed Central
OAI identifier: oai:pubmedcentral.nih.gov:2876182
Provided by: PubMed Central

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Citations

  1. (1998). A novel synaptobrevin/VAMP homologous protein (VAMP5) is increased during in vitro myogenesis and present in the plasma membrane.
  2. (1998). A novel tetanus neurotoxin-insensitive vesicleassociated membrane protein in SNARE complexes of the apical plasma membrane of epithelial cells.
  3. Acritical role for vesicle-associated membrane protein (VAMP)-7 in exocytosis from human eosinophils and neutrophils.
  4. (1996). ARF and PITPrestore GTPgS-stimulated protein secretion from cytosol-depleted HL60 cells by promoting PIP2 synthesis.
  5. Chemoattractant-stimulated Rac activation in wild-type and Rac2-deficient murine neutrophils: preferential activation of Rac2 and Rac2 gene dosage effect on neutrophil functions.
  6. Chronic obstructive pulmonary disease.
  7. (1999). Co-expression of several human syntaxin genes in neutrophils and differentiating HL-60 cells: variant isoforms and detection of syntaxin 1.
  8. Contribution of phospholipase D and a brefeldin A-sensitive ARF to chemoattractant-induced superoxide production and secretion of human neutrophils.
  9. (1993). Control of exocytosis in early neutrophil activation.
  10. Control of vesicle fusion by a tyrosine phosphatase.
  11. (1998). Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 {151} resolution.
  12. Current molecular models for NADPH oxidase regulation by Rac GTPase.
  13. (1999). Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense. Immunity
  14. Divergence of mechanisms regulating respiratory burst in blood and sputum eosinophils and neutrophils from atopic subjects.
  15. (1990). GE: a GTP-binding protein mediating exocytosis. Annu Rev Physiol
  16. (1995). Glucosylation of Rho proteins by Clostridium difficile toxin B.
  17. (1997). Granules of the human neutrophilic polymorphonuclear leukocyte.
  18. GTPases and reactive oxygen species: switches for killing and signaling.
  19. (1996). Identification of a novel syntaxin- and synaptobrevin/VAMP- binding protein, SNAP-23, expressed in non-neuronal tissues.
  20. (2006). Induction of genes mediating interferon-dependent extracellular trap formation during neutrophil differentiation.
  21. Involvement of SNAP-23 and syntaxin 6 in human neutrophil exocytosis.
  22. (1994). Isolation and characterization of gelatinase granules from human neutrophils.
  23. Kinase pathways in chemoattractant-induced degranulation of neutrophils: the role of p38 mitogen-activated protein kinase activated by Src family kinases.
  24. Localization of Rac2 via the C terminus and aspartic acid 150 specifies superoxide generation, actin polarity and chemotaxis in neutrophils. Nat Immunol 2004;5:744–51.Mechanisms of Degranulation in
  25. (1999). Mixed and non-cognate SNARE complexes. Characterization of assembly and biophysical properties.
  26. Molecular basis for Rac2 regulation of phagocyte NADPH oxidase.
  27. (2003). NADPH oxidases: not just for leukocytes anymore! Trends Biochem Sci
  28. (2000). Neurotoxins affecting neuroexocytosis. Physiol Rev
  29. Neutrophil extracellular traps kill bacteria.
  30. Neutrophil primary granule release and maximal superoxide generation depend on Rac2 in a common signalling pathway.
  31. Neutrophilderived matrix metalloproteinase-9 is increased in severe asthma and poorly inhibited by glucocorticoids.
  32. (1999). Neutrophilic leukocytes. In:
  33. Protein-tyrosine phosphatase MEG2 is expressed by human neutrophils. Localization to the phagosome and activation by polyphosphoinositides.
  34. Rac2 is critical for neutrophil primary granule exocytosis.
  35. (1996). Rap, and Rac small GTP-binding proteins are targets for Clostridium sordellii lethal toxin glucosylation.
  36. Rat basophilic leukemia cells express syntaxin-3 and VAMP-7 in granule membranes.
  37. Regulation of tyrosine kinase activation and granule release through beta-arrestin by CXCRI.
  38. (1993). Requirement for posttranslational processing of Rac GTP-binding proteins for activation of human neutrophil NADPH oxidase.
  39. Rho family proteins: coordinating cell responses.
  40. Rho GTPases in cell biology.
  41. Rho-family GTPases: it’s not only Rac and Rho (and I like it).
  42. (1996). Role of beta-arrestin in mediating agonistpromoted G protein-coupled receptor internalization.
  43. Secretory granule exocytosis.
  44. (1993). SNAP receptors implicated in vesicle targeting and fusion.
  45. (1999). SNARE complex formation is triggered by Ca2+ and drives membrane fusion.
  46. Soluble NSF attachment protein receptors (SNAREs) in RBL2H3 mast cells: functional role of syntaxin 4 in exocytosis and identification of a vesicle-associated membrane protein 8-containing secretory compartment.
  47. (1995). Subcellular distribution of docking/fusion proteins in neutrophils, secretory cells with multiple exocytic compartments.
  48. Syntaxin 7 and VAMP-7 are soluble N-ethylmaleimide-sensitive factor attachment protein receptors required for late endosomelysosome and homotypic lysosome fusion in alveolar macrophages.
  49. Syntaxin 7 is localized to late endosome compartments, associates with VAMP8, and is required for late endosome-lysosome fusion.
  50. The sequential release of granule constituents from human neutrophils.
  51. The src-family protein-tyrosine kinase p59hck is located on the secretory granules in human neutrophils and translocates towards the phagosome during cell activation.
  52. (1998). Three novel proteins of the syntaxin/SNAP-25 family.
  53. (1989). Translocation of the FGR protein-tyrosine kinase as a consequence of neutrophil activation.
  54. (1999). VAMP-7 mediates vesicular transport from endosomes to lysosomes.
  55. (1996). VAMP/synaptobrevin isoforms 1 and 2 are widely and differentially expressed in nonneuronal tissues.
  56. (2003). Vesicle trafficking: pleasure and pain from SM genes. Trends Cell Biol
  57. Vesicle-associated membrane protein 3 (VAMP-3) and VAMP-8 are present in human platelets and are required for granule secretion.