Leukocyte-associated immunoglobulin-like receptor-1 is expressed on human megakaryocytes and negatively regulates the maturation of primary megakaryocytic progenitors and cell line
Leukocyte-associated immunoglobulin-like receptor-1 is expressed on human megakaryocytes and negatively regulates the maturation of primary megakaryocytic progenitors and cell line
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白细胞相关免疫球蛋白样受体-1 在人巨核细胞上表达，负向调节原代巨核祖细胞和细胞系的成熟
DOI：
10.1016/j.bbrc.2010.12.140
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发表时间：
2011-02-04
影响因子：
3.1
通讯作者：
Fu, Aili
中科院分区：
文献类型：
--
作者：
Xue, Jiangnan;Zhang, Xiaoshu;Fu, Aili
白细胞相关免疫球蛋白样受体-1(LAIR-1)是一种抑制性胶原受体，属于免疫球蛋白超家族。尽管LAIR-1在多种白细胞中的抑制功能已被广泛描述，但其在巨核细胞(MK)中的作用尚未被研究过。在这里，我们发现LAIR-1在人骨髓CD34(+)、CD41a(+)和CD41a(+)CD42b(+)细胞上表达。LAIR-1也可在人脐血CD34(+)细胞来源的MK中检测到，该MK具有未成熟MK的形态特征。巨核细胞系Dami经佛波酯、佛波酯处理后，LAIR-1膜蛋白表达显著上调。此外，通过MK系特异性标记物(CD41a和CD42b)和多倍化检测，Dami细胞中的LAIR-1与其天然配体或抗LAIR-1抗体的交联导致细胞增殖抑制和PMA促进分化。此外，我们还观察到，LAIR-1的交联会导致在含有TPO的细胞因子混合物中培养的原代人CD34+细胞产生的MK减少。这些结果提示LAIR-1可能是MK分化的早期标志物，并提供了初步证据表明LAIR-1是巨核细胞生成的负调控因子。(C)2011年，由爱思唯尔公司出版。
Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is an inhibitory collagen receptor which belongs to the immunoglobulin (Ig) superfamily. Although the inhibitory function of LAIR-1 has been extensively described in multiple leukocytes, its role in megakaryocyte (MK) has not been explored so far. Here, we show that LAIR-1 is expressed on human bone marrow CD34(+)CD41a(+) and CD41a(+)CD42b(+) cells. LAIR-1 is also detectable in a fraction of human cord blood CD34(+) cell-derived MK that has morphological characteristics of immature MK. In megakaryoblastic cell line Dami, the membrane protein expression of LAIR-1 is up-regulated significantly when cells are treated with phorbol ester phorbol 12-myristate 13-acetate (PMA). Furthermore, cross-linking of LAIR-1 in Dami cells with its natural ligand or anti-LAIR-1 antibody leads to the inhibition of cell proliferation and PMA-promoted differentiation when examined by the MK lineage-specific markers (CD41a and CD42b) and polyploidization. In addition, we also observed that cross-linking of LAIR-1 results in decreased MK generation from primary human CD34+ cells cultured in a cytokines cocktail that contains TPO. These results suggest that LAIR-1 is a likely candidate for an early marker of MK differentiation, and provide initial evidence indicating that LAIR-1 serves as a negative regulator of megakaryocytopoiesis. (c) 2011 Published by Elsevier Inc.