Constitutive mobilization of CD34+ cells into the peripheral blood in idiopathic myelofibrosis may be due to the action of a number of proteases

Mingjiang Xu, Edward Bruno, Joseph Chao, Stephen Huang, Guido Finazzi, Steven M. Fruchtman, Uday Popat, Josef T. Prchal, Giovanni Barosi, Ronald Hoffman

Research output: Contribution to journalArticle

89 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4508-4515
Number of pages8
JournalBlood
Volume105
Issue number11
DOIs
StatePublished - Jun 1 2005
Externally publishedYes

Fingerprint

Primary Myelofibrosis
Matrix Metalloproteinase 9
Leukocyte Elastase
Vascular Cell Adhesion Molecule-1
Blood
Peptide Hydrolases
Conditioned Culture Medium
Matrix Metalloproteinases
Cell Count
Molecular weight
Plasmas
Basement Membrane
Blood Cells
Healthy Volunteers
Molecular Weight

ASJC Scopus subject areas

  • Hematology

Cite this

Constitutive mobilization of CD34+ cells into the peripheral blood in idiopathic myelofibrosis may be due to the action of a number of proteases. / Xu, Mingjiang; Bruno, Edward; Chao, Joseph; Huang, Stephen; Finazzi, Guido; Fruchtman, Steven M.; Popat, Uday; Prchal, Josef T.; Barosi, Giovanni; Hoffman, Ronald.

In: Blood, Vol. 105, No. 11, 01.06.2005, p. 4508-4515.

Research output: Contribution to journalArticle

Xu, M, Bruno, E, Chao, J, Huang, S, Finazzi, G, Fruchtman, SM, Popat, U, Prchal, JT, Barosi, G & Hoffman, R 2005, 'Constitutive mobilization of CD34+ cells into the peripheral blood in idiopathic myelofibrosis may be due to the action of a number of proteases', Blood, vol. 105, no. 11, pp. 4508-4515. https://doi.org/10.1182/blood-2004-08-3238
Xu, Mingjiang ; Bruno, Edward ; Chao, Joseph ; Huang, Stephen ; Finazzi, Guido ; Fruchtman, Steven M. ; Popat, Uday ; Prchal, Josef T. ; Barosi, Giovanni ; Hoffman, Ronald. / Constitutive mobilization of CD34+ cells into the peripheral blood in idiopathic myelofibrosis may be due to the action of a number of proteases. In: Blood. 2005 ; Vol. 105, No. 11. pp. 4508-4515.
@article{df2a8cb95ee048ea80c5bf4b1f07b261,
title = "Constitutive mobilization of CD34+ cells into the peripheral blood in idiopathic myelofibrosis may be due to the action of a number of proteases",
abstract = "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.",
author = "Mingjiang Xu and Edward Bruno and Joseph Chao and Stephen Huang and Guido Finazzi and Fruchtman, {Steven M.} and Uday Popat and Prchal, {Josef T.} and Giovanni Barosi and Ronald Hoffman",
year = "2005",
month = "6",
day = "1",
doi = "10.1182/blood-2004-08-3238",
language = "English (US)",
volume = "105",
pages = "4508--4515",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "11",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=21144457074&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=21144457074&partnerID=8YFLogxK

U2 - 10.1182/blood-2004-08-3238

DO - 10.1182/blood-2004-08-3238

M3 - Article

VL - 105

SP - 4508

EP - 4515

JO - Blood

JF - Blood

SN - 0006-4971

IS - 11

ER -