[en] Engraftment of hematopoietic progenitor cells has been shown to decrease during cell cycle transit. We studied cell cycle-associated changes in adhesion and migration of mitotically activated cord blood CD34+ cells. Migration toward medium conditioned by the stromal-derived factor-1-producing cell line MS-5 was studied in bovine serum albumin- and fibronectin (Fn)-coated transwells. Migration was reduced in cycling CD34+ cells and long-term culture-initiating cells (LTC-ICs) compared with their noncycling counterparts across Fn but not across bovine serum albumin. Conversely, Fn binding was higher in cycling CD34+ cells and LTC-ICs compared with noncycling progenitor cells, while adhesion of both subsets to bovine serum albumin was undetectable. The contribution of alpha4 and alpha5 integrins in mediating adhesion and migration of activated CD34+ cells onto Fn was analyzed by neutralization experiments. While alpha4-mediated Fn binding decreased during G(2)/M, alpha5 integrin-mediated adhesion increased during transit from G(0)/G(1) to S and G(2)/M phases. As for migration, the contribution of alpha4 integrin was similar in all phases, whereas alpha5-directed migration was lower in G(2)/M compared with G(0)/G(1) and S phases. Defective migration of cycling CD34+ cells was not due to differences in alpha5 integrin expression. In conclusion, chemotaxis across Fn is less efficient in cycling progenitor cells in correlation with an increased Fn binding capacity. In addition, alpha4 and alpha5 integrin functions are independently modulated during cell cycle transit.
Disciplines :
Hematology
Author, co-author :
Giet, Olivier ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique
Van Bockstaele, Dirk R
Di Stefano, Ivano
Huygen, Sandra
Greimers, Roland ; Centre Hospitalier Universitaire de Liège - CHU > Anatomie pathologique
Beguin, Yves ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie clinique
Gothot, André ; Centre Hospitalier Universitaire de Liège - CHU > Hématologie biologique et immuno hématologie
Language :
English
Title :
Increased binding and defective migration across fibronectin of cycling hematopoietic progenitor cells.
Publication date :
2002
Journal title :
Blood
ISSN :
0006-4971
eISSN :
1528-0020
Publisher :
American Society of Hematology, Washington, United States - District of Columbia
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