Serum-derived plasminogen is activated by apoptotic cells and promotes their phagocytic clearance

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 fractionatio...

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Published in:The Journal of immunology (1950) 2012-12, Vol.189 (12), p.5722-5728
Main Authors: Rosenwald, Matthias, Koppe, Uwe, Keppeler, Hildegard, Sauer, Guido, Hennel, Roman, Ernst, Anne, Blume, Karin Erika, Peter, Christoph, Herrmann, Martin, Belka, Claus, Schulze-Osthoff, Klaus, Wesselborg, Sebastian, Lauber, Kirsten
Format: Article
Language:English
Subjects:
ABO Blood-Group System - blood
Apoptosis - immunology
Apoptosis Regulatory Proteins - blood
Apoptosis Regulatory Proteins - physiology
Cell Line, Tumor
Chromatography, Affinity - methods
Humans
Macrophages - cytology
Macrophages - immunology
Macrophages - metabolism
Phagocytosis - immunology
Plasminogen - deficiency
Plasminogen - metabolism
Plasminogen - physiology
Primary Cell Culture
Serum - immunology
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1200922