Peripheral blood hematopoietic stem and progenitor cell frequency is unchanged in patients with alpha-1-antitrypsin deficiency.
Int J Hematol
; 99(6): 714-20, 2014 Jun.
Article
en En
| MEDLINE
| ID: mdl-24752699
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Madre Hematopoyéticas
/
Deficiencia de alfa 1-Antitripsina
Tipo de estudio:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Adult
/
Aged
/
Humans
/
Middle aged
Idioma:
En
Revista:
Int J Hematol
Asunto de la revista:
HEMATOLOGIA
Año:
2014
Tipo del documento:
Article
País de afiliación:
Países Bajos