title: P2X7 receptor-mediated scavenger activity of mononuclear phagocytes toward non-opsonized particles and apoptotic cells is inhibited by serum glycoproteins but remains active in cerebrospinal fluid.
abstract: Rapid phagocytosis of non-opsonized particles including apoptotic cells is an important process that involves direct recognition of the target by multiple scavenger receptors including P2X7 on the phagocyte surface. Using a real-time phagocytosis assay, we studied the effect of serum proteins on this phagocytic process. Inclusion of 1-5% serum completely abolished phagocytosis of non-opsonized YG beads by human monocytes. Inhibition was reversed by pretreatment of serum with 1-10 mM tetraethylenepentamine, a copper/zinc chelator. Inhibitory proteins from the serum were determined as negatively charged glycoproteins (pI < 6) with molecular masses between 100 and 300 kDa. A glycoprotein-rich inhibitory fraction of serum not only abolished YG bead uptake but also inhibited phagocytosis of apoptotic lymphocytes or neuronal cells by human monocyte-derived macrophages. Three copper- and/or zinc-containing serum glycoproteins, ceruloplasmin, serum amyloid P-component, and amyloid precursor protein, were identified, and the purified proteins were shown to inhibit the phagocytosis of beads by monocytes as well as phagocytosis of apoptotic neuronal cells by macrophages. Human adult cerebrospinal fluid, which contains very little glycoprotein, had no inhibitory effect on phagocytosis of either beads or apoptotic cells. These data suggest for the first time that metal-interacting glycoproteins present within serum are able to inhibit the scavenger activity of mononuclear phagocytes toward insoluble debris and apoptotic cells.
authors.affiliation: Florey Neuroscience Institutes, University of Melbourne, Parkville, Victoria 3010.
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Gu
authors.affiliation: Mental Health Research Institute, Melbourne Brain Centre, University of Melbourne, Parkville, Victoria 3010.
authors.forename: James A
authors.initials: JA
authors.lastname: Duce
authors.affiliation: Cell Signalling Unit, Children's Medical Research Institute, University of Sydney, Wentworthville, New South Wales 2145, Australia.
authors.forename: Valentina A
authors.initials: VA
authors.lastname: Valova
authors.affiliation: Mental Health Research Institute, Melbourne Brain Centre, University of Melbourne, Parkville, Victoria 3010.
authors.forename: Bruce
authors.initials: B
authors.lastname: Wong
authors.affiliation: Mental Health Research Institute, Melbourne Brain Centre, University of Melbourne, Parkville, Victoria 3010.
authors.forename: Ashley I
authors.initials: AI
authors.lastname: Bush
authors.affiliation: Florey Neuroscience Institutes, University of Melbourne, Parkville, Victoria 3010; Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Victoria 3010.
authors.forename: Steven
authors.initials: S
authors.lastname: Petrou
authors.affiliation: Florey Neuroscience Institutes, University of Melbourne, Parkville, Victoria 3010. Electronic address: james.wiley@florey.edu.au.
authors.forename: James S
authors.initials: JS
authors.lastname: Wiley
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D001798:Blood Proteins / Q000378:metabolism*; D002555:Cerebrospinal Fluid / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010587:Phagocytosis / Q000502:physiology*; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*
chemical_list: D001798:Blood Proteins; D058486:Receptors, Purinergic P2X7