title: The role of annexin A5 in the modulation of the immune response against dying and dead cells.
abstract: Annexins are characterized by the ability to bind phospholipids of membranes in the presence of Ca2+. Annexin A5 represents a typical member of this protein family and is a natural occurring highly specific ligand for phosphatidylserine (PS). The exposure of PS is one major "eat me" signal for phagocytes of apoptotic and necrotic cells. Apoptotic cells are normally cleared via an anti-inflammatory pathway. In contrast, the uptake and removal of necrotic cells normally involves inflammation and an immune response. Interestingly, the lack of endogenous annexin A5 also leads to a reduced inflammatory potential of necrotic cells. Annexin A5 may interfere in vivo with the immunosuppressive effects of apoptotic cells since it preferentially binds PS with high affinity and inhibits apoptotic cell uptake by macrophages. In this review we focus on how defects in the clearance process can lead to chronic autoimmunity. Furthermore, the role of annexin A5 as important adjuvant for apoptotic cell-based tumour vaccines is discussed. The mechanism of how the immunogenicity of apoptotic cells can be restored by blocking their PS-dependent clearance is outlined in detail. Taken together, annexin A5 is an important modulator of the immune response against PS-exposing particles like apoptotic cells, necrotic cells, and certain viruses.
authors.affiliation: Institute for Clinical Immunology and Exp. Medicine I, Friedrich-Alexander-University of Erlangen-Nuremberg, Glückstrasse 4a and 6, 91054 Erlangen, Germany.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Munoz
authors.forename: Benjamin
authors.initials: B
authors.lastname: Frey
authors.forename: Friederike
authors.initials: F
authors.lastname: Pausch
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Baum
authors.forename: Ruediger B
authors.initials: RB
authors.lastname: Mueller
authors.forename: Bent
authors.initials: B
authors.lastname: Brachvogel
authors.forename: Ernst
authors.initials: E
authors.lastname: Poschl
authors.forename: Franz
authors.initials: F
authors.lastname: Rödel
authors.forename: Klaus
authors.initials: K
authors.lastname: von der Mark
authors.forename: Martin
authors.initials: M
authors.lastname: Herrmann
authors.forename: Udo S
authors.initials: US
authors.lastname: Gaipl
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000502:physiology*; D017209:Apoptosis / Q000276:immunology; D016923:Cell Death / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D008264:Macrophages / Q000502:physiology; D009336:Necrosis / Q000276:immunology; D009369:Neoplasms / Q000276:immunology / Q000473:pathology; D010587:Phagocytosis / Q000276:immunology*; D010718:Phosphatidylserines / Q000502:physiology
chemical_list: D017304:Annexin A5; D010718:Phosphatidylserines