PMID- 24752699
OWN - NLM
STAT- MEDLINE
DCOM- 20150413
LR  - 20211021
IS  - 1865-3774 (Electronic)
IS  - 0925-5710 (Linking)
VI  - 99
IP  - 6
DP  - 2014 Jun
TI  - Peripheral blood hematopoietic stem and progenitor cell frequency is unchanged in 
      patients with alpha-1-antitrypsin deficiency.
PG  - 714-20
LID - 10.1007/s12185-014-1581-3 [doi]
AB  - Granulocyte-colony-stimulating factor (G-CSF)-induced hematopoietic stem and 
      progenitor cell (HSPC) mobilization is associated with the release of 
      neutrophil-derived proteases. Previously, we have shown that alpha-1-antitrypsin 
      (AAT) inhibits these proteases in mice, resulting in inhibition of HSPC 
      mobilization. Here, we studied the relationship between AAT and HSPC in steady 
      state and cytokine-induced mobilization in humans. Patients with 
      alpha-1-antitrypsin deficiency (AATD) have an 85-90 % decrease of AAT in the 
      peripheral blood (PB). We hypothesized that this leads to increased proteolytic 
      activity in the bone marrow and increased steady-state PB HSPC numbers. Using 
      flow cytometry and semi-solid cell culture, we found no significant difference in 
      PB HSPC in AATD patients (n = 18) as compared to controls (n = 22). Healthy stem 
      cell donors (n = 43) were mobilized with G-CSF for 5 days and the number of 
      CD45(+)/CD34(+) HSPC were determined in PB. We found that, during mobilization, 
      PB AAT levels increased significantly, positively correlating with PB 
      CD45(+)/CD34(+) cells (r = 0.31, p = 0.005). In conclusion, although serum AAT 
      levels and HSPC mobilization in healthy stem cell donors are positively 
      correlated, AAT is not an indispensable protease-inhibitor in the constitutive 
      circulation of HSPC. These findings suggest a model in which both 
      protease-dependent and -independent pathways contribute to HSPC mobilization.
FAU - de Kruijf, Evert-Jan F M
AU  - de Kruijf EJ
AD  - Department of Immunohematology and Blood Transfusion, Leiden University Medical 
      Center, PO Box 9600, 2300 RC, Leiden, The Netherlands.
FAU - Alkemade, Gonnie M
AU  - Alkemade GM
FAU - van Os, Ronald
AU  - van Os R
FAU - Fibbe, Willem E
AU  - Fibbe WE
FAU - van Pel, Melissa
AU  - van Pel M
LA  - eng
PT  - Journal Article
DEP - 20140422
PL  - Japan
TA  - Int J Hematol
JT  - International journal of hematology
JID - 9111627
RN  - 0 (Autoantibodies)
RN  - 0 (alpha 1-Antitrypsin)
RN  - 143011-72-7 (Granulocyte Colony-Stimulating Factor)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Autoantibodies/blood/immunology
MH  - Case-Control Studies
MH  - Cell Count
MH  - Granulocyte Colony-Stimulating Factor/pharmacology
MH  - Hematopoietic Stem Cell Mobilization/methods
MH  - Hematopoietic Stem Cells/*cytology/drug effects
MH  - Humans
MH  - Middle Aged
MH  - Phenotype
MH  - Young Adult
MH  - alpha 1-Antitrypsin/blood/immunology
MH  - alpha 1-Antitrypsin Deficiency/*blood
EDAT- 2014/04/23 06:00
MHDA- 2015/04/14 06:00
CRDT- 2014/04/23 06:00
PHST- 2013/11/22 00:00 [received]
PHST- 2014/04/03 00:00 [accepted]
PHST- 2014/04/02 00:00 [revised]
PHST- 2014/04/23 06:00 [entrez]
PHST- 2014/04/23 06:00 [pubmed]
PHST- 2015/04/14 06:00 [medline]
AID - 10.1007/s12185-014-1581-3 [doi]
PST - ppublish
SO  - Int J Hematol. 2014 Jun;99(6):714-20. doi: 10.1007/s12185-014-1581-3. Epub 2014 
      Apr 22.