Peripheral blood hematopoietic stem and progenitor cell frequency is unchanged in patients with alpha-1-antitrypsin deficiency

Evert-Jan F. M. de Kruijf, Gonnie M. Alkemade, Ronald van Os, Willem E. Fibbe, Melissa van Pel*

*Corresponding author for this work

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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.

Original languageEnglish
Pages (from-to)714-720
Number of pages7
JournalInternational journal of hematology
Issue number6
Publication statusPublished - Jun-2014


  • Stem cells
  • Alpha-1-antitrypsin deficiency
  • Hematopoietic stem cell mobilization
  • Granulocyte-colony-stimulating factor
  • G-CSF
  • MICE

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