Plasmin Is A Chemoattractant For Immature Dendritic Cells Acting Through Akt2-Dependent Mechanisms

Pivotal roles have been proposed for dendritic cells (DCs) and the adaptive immune response in atherosclerosis. Here we demonstrate that plasmin is a potent activator of human DCs. Stimulation of immature DCs with plasmin, but not with catalytically inactivated plasmin, elicits actin polymerization and a chemotactic cell migration comparable to that triggered by the standard chemoattractant FMLP. Plasmin‐stimulated DCs show rapid activation of Akt, ERK1/2 and p38 MAP kinases, followed by phosphorylation of the regulatory myosin light chain and chemotaxis. DCs express Akt1 and Akt2, yet plasmin activates exclusively Akt2 via a p38 MAPK‐dependent pathway. Knockdown of Akt2, but not of Akt1 by shRNA inhibited the plasmin‐induced ERK1/2 activation and the chemotaxis. Using immunohistochemistry we show that both, plasmin and DCs, are abundant in human atherosclerotic lesions, where they colocalize. Therefore, this novel link between protease activity and the adaptive immune response may be of particular relevance in atherogenesis.