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Blood, 1 March 2001, Vol. 97, No. 5, pp. 1282-1288
HEMATOPOIESIS
Synergistic mobilization of hemopoietic progenitor cells using
concurrent 1 and 2 integrin blockade or 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
4 1 integrin in this process. To test whether mobilization
involves dynamic interactions of 4 1 with other integrins on
hematopoietic cells, especially the 2 integrins, mice and primates
were treated with anti- 1 or anti- 2 antibodies alone or in
combination. A single injection of anti- 4 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- 2 (anti-CD11a or anti-CD18) or
anti- 5/ 1 integrin antibody was combined with anti- 4, an
augmentation in mobilization was seen that was either additive or
synergistic, depending on the potency of the antibody used. Synergy
between anti- 4 and anti-CD18 ( 2) antibody blockade
was seen in primates and confirmed in anti- 4-treated CD18-deficient
mice. In the latter, there was a 49-fold increase in mobilization with
anti- 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 4 1 with 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 1 and 2 integrin crosstalk in stem/progenitor
cell mobilization.

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