TY - JOUR
T1 - Constitutive mobilization of CD34+ cells into the peripheral blood in idiopathic myelofibrosis may be due to the action of a number of proteases
AU - Xu, Mingjiang
AU - Bruno, Edward
AU - Chao, Joseph
AU - Huang, Stephen
AU - Finazzi, Guido
AU - Fruchtman, Steven M.
AU - Popat, Uday
AU - Prchal, Josef T.
AU - Barosi, Giovanni
AU - Hoffman, Ronald
PY - 2005/6/1
Y1 - 2005/6/1
N2 - Idiopathic myelofibrosis (IM) is characterized by increased numbers of CD34+ cells in the peripheral blood (PB). We explored the possible mechanisms underlying this abnormal trafficking of CD34+ cells. Plasma levels of neutrophil elastase (NE), total and active matrix metalloproteinase 9 (MMP-9), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were dramatically increased in IM. The absolute number of CD34 + cells in the PB was correlated with the levels of sVCAM-1. Marked elevations of the levels of NE but not total and active MMP-9 as well as MMP-2 were detected in media conditioned by IM mononuclear cells (MNCs) as compared with that of healthy volunteers. IM MNC-conditioned media, however, was shown by zymographic analysis to contain increased gelatinolytic activity corresponding to the molecular weight of MMP-9. IM MNC-conditioned media also exhibited a greater ability to cleave VCAM-1 and c-kit in vitro, consistent with the biologic actions of NE. In addition, the increased ability of IM PB CD34 + cells to migrate through a reconstituted basement membrane was diminished by several inhibitors of MMP-9 activity, indicating that these cells express increased levels of this MMP. These data indicate that a proteolytic environment exists in IM which might result in the sustained mobilization of CD34+ cells.
AB - Idiopathic myelofibrosis (IM) is characterized by increased numbers of CD34+ cells in the peripheral blood (PB). We explored the possible mechanisms underlying this abnormal trafficking of CD34+ cells. Plasma levels of neutrophil elastase (NE), total and active matrix metalloproteinase 9 (MMP-9), and soluble vascular cell adhesion molecule-1 (sVCAM-1) were dramatically increased in IM. The absolute number of CD34 + cells in the PB was correlated with the levels of sVCAM-1. Marked elevations of the levels of NE but not total and active MMP-9 as well as MMP-2 were detected in media conditioned by IM mononuclear cells (MNCs) as compared with that of healthy volunteers. IM MNC-conditioned media, however, was shown by zymographic analysis to contain increased gelatinolytic activity corresponding to the molecular weight of MMP-9. IM MNC-conditioned media also exhibited a greater ability to cleave VCAM-1 and c-kit in vitro, consistent with the biologic actions of NE. In addition, the increased ability of IM PB CD34 + cells to migrate through a reconstituted basement membrane was diminished by several inhibitors of MMP-9 activity, indicating that these cells express increased levels of this MMP. These data indicate that a proteolytic environment exists in IM which might result in the sustained mobilization of CD34+ cells.
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U2 - 10.1182/blood-2004-08-3238
DO - 10.1182/blood-2004-08-3238
M3 - Article
C2 - 15705794
AN - SCOPUS:21144457074
SN - 0006-4971
VL - 105
SP - 4508
EP - 4515
JO - Blood
JF - Blood
IS - 11
ER -