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Role of vesicle-associated membrane protein-2, through Q-soluble N-ethylmaleimide-sensitive factor attachment protein receptor/R-soluble N-ethylmaleimide-sensitive factor attachment protein receptor interaction, in the exocytosis of specific and tertiary granules of human neutrophils.

We have examined the role of the R-soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) synaptobrevin-2/vesicle-associated membrane protein (VAMP)-2 in neutrophil exocytosis. VAMP-2, localized in the membranes of specific and gelatinase-containing tertiary granules in resting human neutrophils, resulted translocated to the cell surface following neutrophil activation under experimental conditions that induced exocytosis of specific and tertiary granules. VAMP-2 was also found on the external membrane region of granules docking to the plasma membrane in activated neutrophils. Specific Abs against VAMP-2 inhibited Ca(2+) and GTP-gamma-S-induced exocytosis of CD66b-enriched specific and tertiary granules, but did not affect exocytosis of CD63-enriched azurophilic granules, in electropermeabilized neutrophils. Tetanus toxin disrupted VAMP-2 and inhibited exocytosis of tertiary and specific granules. Activation of neutrophils led to the interaction of VAMP-2 with the plasma membrane Q-SNARE syntaxin 4, and anti-syntaxin 4 Abs inhibited exocytosis of specific and tertiary granules in electropermeabilized neutrophils. Immunoelectron microscopy showed syntaxin 4 on the plasma membrane contacting with docked granules in activated neutrophils. These data indicate that VAMP-2 mediates exocytosis of specific and tertiary granules, and that Q-SNARE/R-SNARE complexes containing VAMP-2 and syntaxin 4 are involved in neutrophil exocytosis.

Pubmed ID: 12517971


  • Mollinedo F
  • Martín-Martín B
  • Calafat J
  • Nabokina SM
  • Lazo PA


Journal of immunology (Baltimore, Md. : 1950)

Publication Data

January 15, 2003

Associated Grants


Mesh Terms

  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Neoplasm
  • Arginine
  • Cell Adhesion Molecules
  • Cell Membrane Permeability
  • Conserved Sequence
  • Cytoplasmic Granules
  • Electroporation
  • Exocytosis
  • GPI-Linked Proteins
  • Glutamine
  • Humans
  • Interphase
  • Membrane Proteins
  • Microscopy, Immunoelectron
  • Molecular Sequence Data
  • Neutrophil Activation
  • Neutrophils
  • Qa-SNARE Proteins
  • R-SNARE Proteins
  • SNARE Proteins
  • Solubility
  • Tetanus Toxin
  • Vesicular Transport Proteins