Granulocyte-macrophage colony-stimulating factor (GM-CSF) increases plasma fibrinolytic activity in vivo

Abstract

Increased phagocyte adhesion to vascular endothelium in response to granulocyte-macrophage colony-stimulating factor (GM-CSF) administration may affect endothelial integrity and functions such as the expression of fibrinolytic properties. In patients with lymphoma receiving GM-CSF (30 μg/m 2 over 2 h), over-all plasma fibrinolytic activity, as measured by fibrin plate assays, increased from 78±15% to 118±35% (p<0.05, n=4), while tissue plasminogen activator (t-PA) levels increased from 0.35±0.10 IU/mL to 1.14±0.2 IU/mL (245±139% over preinfusion levels, p<0.05) by the end of the infusion. This was accompanied by a rise in t-PA antigen levels to 50±32% above baseline (p<0.05), and a corresponding fall in plasminogen activator inhibitor levels from 14.5±3.2 IU/mL to 6.8±2.9 IU/mL (52±25% of baseline, p<0.05). In contrast, macrophage colony-stimulating factor (M-CSF), which activates and primes mononuclear phagocytic cells, but does not increase cell adherence to endothelium, has no effect on plasma fibrinolytic parameters at these times. Increased plasma t-PA activity following GM-CSF administration suggests an indirect effect on endothelial function in vivo, and may be relevant to the reported side effects of GM-CSF such as the capillary leak syndrome, as well as to the chronic bleeding seen in GM-CSF transgenic mice.