期刊
BLOOD
卷 97, 期 5, 页码 1282-1288出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood.V97.5.1282
关键词
-
类别
资金
- NCRR NIH HHS [RR00166] Funding Source: Medline
- NIAID NIH HHS [AI32177] Funding Source: Medline
- NIDDK NIH HHS [DK46557] Funding Source: Medline
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 alpha4 beta1 integrin in this process. To test whether mobilization involves dynamic interactions of alpha4 beta1 with other integrins on hematopoietic cells, especially the beta2 integrins, mice and primates were treated with anti-beta1 or anti-beta2 antibodies alone or in combination. A single injection of anti-alpha4 beta1 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-beta2 (anti-CD11a or anti-CD18) or anti-alpha5/beta1 integrin antibody was combined with anti-alpha4, an augmentation in mobilization was seen that was either additive or synergistic, depending on the potency of the antibody used. Synergy between anti-alpha4 and anti-CD18 (beta (2)) antibody blockade was seen in primates and confirmed in anti-alpha4-treated CD18-deficient mice, In the latter, there was a 49-fold increase in mobilization with anti-alpha4, 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 alpha4 beta1 with beta2 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 beta1 and beta2 integrin crosstalk in stem/progenitor cell mobilization. (Blood, 2001;97:1282-1288) (C) 2001 by The American Society of Hematology.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据