title: Serum-derived plasminogen is activated by apoptotic cells and promotes their phagocytic clearance.
abstract: The elimination of apoptotic cells, called efferocytosis, is fundamentally important for tissue homeostasis and prevents the onset of inflammation and autoimmunity. Serum proteins are known to assist in this complex process. In the current study, we performed a multistep chromatographic fractionation of human serum and identified plasminogen, a protein involved in fibrinolysis, wound healing, and tissue remodeling, as a novel serum-derived factor promoting apoptotic cell removal. Even at levels significantly lower than its serum concentration, purified plasminogen strongly enhanced apoptotic prey cell internalization by macrophages. Plasminogen acted mainly on prey cells, whereas on macrophages no enhancement of the engulfment process was observed. We further demonstrate that the efferocytosis-promoting activity essentially required the proteolytic activation of plasminogen and was completely abrogated by the urokinase plasminogen activator inhibitor-1 and serine protease inhibitor aprotinin. Thus, our study assigns a new function to plasminogen and plasmin in apoptotic cell clearance.
authors.affiliation: Department of Internal Medicine I, University of Tuebingen, 72076 Tuebingen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Rosenwald
authors.forename: Uwe
authors.initials: U
authors.lastname: Koppe
authors.forename: Hildegard
authors.initials: H
authors.lastname: Keppeler
authors.forename: Guido
authors.initials: G
authors.lastname: Sauer
authors.forename: Roman
authors.initials: R
authors.lastname: Hennel
authors.forename: Anne
authors.initials: A
authors.lastname: Ernst
authors.forename: Karin Erika
authors.initials: KE
authors.lastname: Blume
authors.forename: Christoph
authors.initials: C
authors.lastname: Peter
authors.forename: Martin
authors.initials: M
authors.lastname: Herrmann
authors.forename: Claus
authors.initials: C
authors.lastname: Belka
authors.forename: Klaus
authors.initials: K
authors.lastname: Schulze-Osthoff
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wesselborg
authors.forename: Kirsten
authors.initials: K
authors.lastname: Lauber
mesh_terms: D000017:ABO Blood-Group System / Q000097:blood; D017209:Apoptosis / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins / Q000097:blood / Q000502:physiology*; D045744:Cell Line, Tumor; D002846:Chromatography, Affinity / Q000379:methods; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology*; D010958:Plasminogen / Q000172:deficiency / Q000378:metabolism* / Q000502:physiology; D061251:Primary Cell Culture; D044967:Serum / Q000276:immunology
chemical_list: D000017:ABO Blood-Group System; D051017:Apoptosis Regulatory Proteins; D010958:Plasminogen