Plasmin therapy enhances mobilization of HPCs after G-CSF.
The role of proteinases in the mobilization of hematopoietic progenitor cells (HPCs) after granulocyte colony-stimulating factor (G-CSF) remains unclear. Here we report that genetic loss of the plasminogen activator inhibitor Pai-1 or of the plasmin inhibitor alpha2-antiplasmin increases HPC mobilization in response to G-CSF. Moreover, thrombolytic agents, such as tenecteplase and microplasmin, enhance HPC mobilization in mice and humans. Taken together, these findings identify a novel role for plasmin in augmenting HPC mobilization in response to G-CSF.
Tjwa
Marc
M
Vesalius Research Center, Leuven, Belgium.
Janssens
Stefan
S
Carmeliet
Peter
P
D000818:Animals; D005260:Female; D005341:Fibrinolysin / Q000008:administration & dosage*; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D008297:Male; D051379:Mice; D010446:Peptide Fragments / Q000008:administration & dosage; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D058258:Serpin E2; D015843:Serpins / Q000235:genetics / Q000378:metabolism; D000077785:Tenecteplase; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage; D000979:alpha-2-Antiplasmin / Q000235:genetics / Q000378:metabolism
D005343:Fibrinolytic Agents; D010446:Peptide Fragments; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D058258:Serpin E2; C511869:Serpine2 protein, mouse; D015843:Serpins; D000979:alpha-2-Antiplasmin; D016179:Granulocyte Colony-Stimulating Factor; C054561:microplasmin; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D000077785:Tenecteplase