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Blood, 1 March 2001, Vol. 97, No. 5, pp. 1282-1288

HEMATOPOIESIS

Synergistic mobilization of hemopoietic progenitor cells using concurrent beta 1 and beta 2 integrin blockade or beta 2-deficient mice

Thalia Papayannopoulou, Gregory V. Priestley, Betty Nakamoto, Vivian Zafiropoulos, Linda M. Scott, and John M. Harlan

From the University of Washington, Seattle, WA.

The hierarchy of cytoadhesion molecules involved in hematopoietic/stem progenitor cell mobilization has not yet been delineated. Previous studies have suggested an important role for alpha 4beta 1 integrin in this process. To test whether mobilization involves dynamic interactions of alpha 4beta 1 with other integrins on hematopoietic cells, especially the beta 2 integrins, mice and primates were treated with anti-beta 1 or anti-beta 2 antibodies alone or in combination. A single injection of anti-alpha 4beta 1 antibody elicited reproducible mobilization in contrast to other antibodies, and 3 injections yielded higher mobilization efficiency than each of the other antibodies. When the anti-beta 2 (anti-CD11a or anti-CD18) or anti-alpha 5/beta 1 integrin antibody was combined with anti-alpha 4, an augmentation in mobilization was seen that was either additive or synergistic, depending on the potency of the antibody used. Synergy between anti-alpha 4 and anti-CD18 (beta 2) antibody blockade was seen in primates and confirmed in anti-alpha 4-treated CD18-deficient mice. In the latter, there was a 49-fold increase in mobilization with anti-alpha 4, much higher than in littermate control animals, in CD18 hypomorphic mice, or in other strains of mice tested. Data from both the antibody blockade and gene-targeted mice suggest that the cooperativity of alpha 4beta 1 with beta 2 integrins becomes evident when they are concurrently inhibited. It is unclear whether this cooperativity is exerted at the stage of reversible adhesion versus migration, and enhancement of and whether the 2 integrins work in a sequential or parallel manner. Whatever the mechanism, the data provide a novel example of beta 1 and beta 2 integrin crosstalk in stem/progenitor cell mobilization.

© 2001 by The American Society of Hematology.
 

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  Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020