Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• International journal of hematology, 2014-06, Vol.99 (6), p.714-720

Ort / Verlag

Tokyo: Springer Japan

Erscheinungsjahr

2014

Quelle

2022 ECC(Springer)

Beschreibungen/Notizen

• 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.