CD34 and CD43 inhibit mast cell adhesion and are required for optimal mast cell reconstitution

CD34 and CD43 inhibit mast cell adhesion and are required for optimal mast cell reconstitution
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DOI:
10.1016/j.immuni.2004.11.014
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发表时间:
2005-01-01
期刊:
影响因子:
32.4
通讯作者:
McNagny, KM
McNagny, KM
中科院分区:
医学1区
文献类型:
--
作者:
Drew, E;Merzaban, JS;McNagny, KM

文献摘要

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CD 34是一种由造血干细胞(HSC)、肥大细胞和血管内皮细胞表达的细胞表面唾液粘蛋白。尽管CD 34作为HSC标志物很受欢迎,但其在造血细胞上的功能仍然是个谜。在这里,我们已经解决了这个问题,通过检查的行为突变肥大细胞缺乏CD 34,相关的唾液酸粘蛋白,CD 43,或这两种分子。这些分子的缺失导致肥大细胞同型聚集的基因剂量依赖性增加,其中CD 34/CD 43 KO> CD 43 KO> CD 34 KO>野生型。重要的是,这些细胞中CD 34或CD 43的再表达引起这种表型的逆转。此外,我们发现,这些唾液酸粘蛋白的损失,防止肥大细胞再增殖和造血前体重建体内。我们的数据为CD 34的造血功能提供了明确的证据,并表明它是细胞粘附的负调节因子。
CD34 is a cell-surface sialomucin expressed by hematopoietic stem cells (HSC), mast cells, and vascular endothelia. Despite its popularity as an HSC marker, the function of CD34 on hematopoietic cells remains enigmatic. Here, we have addressed this issue by examining the behavior of mutant mast cells lacking CD34, the related sialomucin, CD43, or both molecules. Loss of these molecules leads to a gene-dose-dependent increase in mast cell homotypic aggregation with CD34/CD43KOs > CD43KO > CD34KO > wild-type. Importantly, reexpression of CD34 or CD43 in these cells caused reversal of this phenotype. Furthermore, we find that loss of these sialomucins prevents mast cell repopulation and hematopoietic precursor reconstitution in vivo. Our data provide clear-cut evidence for a hematopoietic function for CD34 and suggest that it acts as a negative regulator of cell adhesion.