title: Peripheral blood hematopoietic stem and progenitor cell frequency is unchanged in patients with alpha-1-antitrypsin deficiency.
abstract: 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.
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands.
authors.forename: Evert-Jan F M
authors.initials: EJ
authors.lastname: de Kruijf
authors.forename: Gonnie M
authors.initials: GM
authors.lastname: Alkemade
authors.forename: Ronald
authors.initials: R
authors.lastname: van Os
authors.forename: Willem E
authors.initials: WE
authors.lastname: Fibbe
authors.forename: Melissa
authors.initials: M
authors.lastname: van Pel
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D016022:Case-Control Studies; D002452:Cell Count; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D010641:Phenotype; D055815:Young Adult; D000515:alpha 1-Antitrypsin / Q000097:blood / Q000276:immunology; D019896:alpha 1-Antitrypsin Deficiency / Q000097:blood*
chemical_list: D001323:Autoantibodies; D000515:alpha 1-Antitrypsin; D016179:Granulocyte Colony-Stimulating Factor
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