title: Specific granules of human eosinophils have lysosomal characteristics: presence of lysosome-associated membrane proteins and acidification upon cellular activation.
abstract: Eosinophils possess characteristic specific granules. Their content may be important during host defense but it can also cause damage after release at sites of inflammation. We investigated possible lysosomal characteristics of these granules. Lysosome-associated membrane protein (LAMP)-1 and 2, were detected by Western blot, subcellular fractionation, and immunoelectron microscopy (IEM) and were localized to the membrane of specific granules and in vesicles of the cytoplasm, separate from secretory vesicles. No binding of mannose 6-phosphate receptor to proteins of specific granules could be detected, indicating that they are dephosphorylated and mature. Cellular activation by interleukin-5 caused acidification of specific granules, as detected by pH-dependent probes. The acidification was inhibited by concanamycin A (inhibitor of vacuolar H(+)-ATPase). Activation of eosinophils by serum-treated zymosan (STZ) caused degranulation into STZ-containing phagosomes and incorporation of LAMPs to their membranes. In conclusion, specific granules of eosinophils can be regarded as specialized primary lysosomes, a feature that may be important for their function and integrity.
authors.affiliation: Department of Medical Microbiology, Malmö University Hospital, Malmö, Sweden. terese.persson@mikrobiol.mas.lu.se
authors.forename: Terese
authors.initials: T
authors.lastname: Persson
authors.forename: Jero
authors.initials: J
authors.lastname: Calafat
authors.forename: Hans
authors.initials: H
authors.lastname: Janssen
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Karawajczyk
authors.forename: Sven R
authors.initials: SR
authors.lastname: Carlsson
authors.forename: Arne
authors.initials: A
authors.lastname: Egesten
mesh_terms: D015703:Antigens, CD / Q000032:analysis / Q000276:immunology; D003593:Cytoplasm / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000737:chemistry* / Q000648:ultrastructure; D004804:Eosinophils / Q000737:chemistry* / Q000648:ultrastructure; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051907:Lysosomal Membrane Proteins; D008247:Lysosomes / Q000737:chemistry* / Q000648:ultrastructure; D008562:Membrane Glycoproteins / Q000032:analysis / Q000276:immunology; D008565:Membrane Proteins / Q000032:analysis; D016253:Microscopy, Immunoelectron; D010587:Phagocytosis; D010588:Phagosomes / Q000737:chemistry / Q000648:ultrastructure; D017527:Receptor, IGF Type 2 / Q000032:analysis
chemical_list: D015703:Antigens, CD; D051907:Lysosomal Membrane Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D017527:Receptor, IGF Type 2