title: Annexin I is stored within gelatinase granules of human neutrophil and mobilized on the cell surface upon adhesion but not phagocytosis.
abstract: Annexin I, a member of the calcium- and phospholipid-binding annexin superfamily of proteins, is largely present in human neutrophils. To determine its exact intracellular distribution a combination of flow cytometry, confocal microscopy and electron microscopy analyses were performed on resting human neutrophils as well as on cells which had been activated. In resting neutrophils, annexin I was found to be present in small amounts in the nucleus, in the cytoplasm and partially also associated with the plasma membrane. The cytoplasmic pool of annexin I was predominant, and the protein was co-localized with gelatinase (marker of gelatinase granules), but not with human serum albumin or CD35 (markers of secretory vesicles), or with lysosomes. Electron microscopy showed the presence of annexin I inside the gelatinase granules. Neutrophil adhesion to monolayers of endothelial cells, but not phagocytosis of particles of opsonized zymosan, provoked an intense mobilization of annexin I, with a marked externalization on the outer leaflet of the plasma membrane. Remaining intracellular annexin I was also found in proximity of the plasma membrane. These results provide a novel mechanism for annexin I secretion from human neutrophils, which is via a degranulation event involving gelatinase granules.
authors.affiliation: Department of Biochemical Pharmacology, The William Harvey Research Institute, St. Bartholomew's and The Royal London School of Medicine and Dentistry, Charterhouse Square, London, UK. m.perretti@qmw.ac.uk
authors.forename: M
authors.initials: M
authors.lastname: Perretti
authors.forename: H
authors.initials: H
authors.lastname: Christian
authors.forename: S K
authors.initials: SK
authors.lastname: Wheller
authors.forename: I
authors.initials: I
authors.lastname: Aiello
authors.forename: K G
authors.initials: KG
authors.lastname: Mugridge
authors.forename: J F
authors.initials: JF
authors.lastname: Morris
authors.forename: R J
authors.initials: RJ
authors.lastname: Flower
authors.forename: N J
authors.initials: NJ
authors.lastname: Goulding
mesh_terms: D017305:Annexin A1 / Q000378:metabolism*; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D018093:Gelatinases / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D010587:Phagocytosis / Q000276:immunology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D017305:Annexin A1; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D018093:Gelatinases