Plasmin on adherent cells: from microvesiculation to apoptosis

Loïc Doeuvre , Laurent Plawinski , Didier Goux , Denis Vivien , Eduardo Anglés-Cano (1)

1 Sérine protéases et physiopathologie de l'unité neurovasculaire

Cell activation by stressors is characterised by a sequence of detectable phenotypic cell changes. A given stimulus, depending on its strength, induces modifications in the activity of membrane phospholipid transporters and calpains, which lead to phosphatidylserine exposure, membrane blebbing and the release of microparticles (nanoscale membrane vesicles). This vesiculation could be considered as a warning signal that may be followed, if the stimulus is maintained, by cell detachment-induced apoptosis. In this study, plasminogen incubated with adherent cells is converted into plasmin by constitutively expressed tPA or uPA. Plasmin formed on the cell membrane then induces a unique response characterized by membrane blebbing and vesiculation. Hitherto unknown for plasmin, these membrane changes are similar to those induced by thrombin on platelets. If plasmin formation persists, matrix proteins are then degraded, cells lose their attachments and enter the apoptotic process, characterized by DNA fragmentation and specific ultrastructural features. Since other proteolytic or inflammatory stimuli may evoke similar responses in different types of adherent cells, the proposed experimental procedure can be used to distinguish activated adherent cells from cells entering the apoptotic process. Such a distinction is crucial for evaluating effects of mediators, inhibitors and potential therapeutic agents.

Mots clés: Life Sciences

Loïc Doeuvre, Laurent Plawinski, Didier Goux, Denis Vivien, Eduardo Anglés-Cano. Plasmin on adherent cells: from microvesiculation to apoptosis. Biochemical Journal, 2010, 432 (2), pp.365-373. ⟨10.1042/BJ20100561⟩. ⟨hal-00535582⟩