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

J Immunol. 2012 Dec 15;189(12):5722-8. doi: 10.4049/jimmunol.1200922. Epub 2012 Nov 12.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • ABO Blood-Group System
  • Apoptosis Regulatory Proteins
  • Plasminogen