Alzheimer's amyloid precursor protein is expressed on the surface of hematopoietic cells upon activation

Alzheimer's amyloid precursor protein is expressed on the surface of hematopoietic cells upon activation
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DOI:
10.1016/0167-4889(96)00015-8
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发表时间:
1996-08-21
影响因子:
5.1
通讯作者:
Valdivieso, F
Valdivieso, F
中科院分区:
生物学2区
文献类型:
--
作者:
Bullido, MJ;MunozFernandez, MA;Valdivieso, F

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a4 -淀粉样蛋白是在阿尔茨海默病患者大脑中发现的老年斑和神经原纤维缠结的主要成分。这种39-42个氨基酸的肽来源于一个较大的前体蛋白(APP)。由于APP基因编码一种假定的膜蛋白,因此研究APP在细胞表面的表达可能为了解其生理功能提供有用的数据。在本报告中,我们提供了APP表达的数据,这些数据是通过造血系统细胞中APP特异性单克隆抗体检测到的。APP在静息的人淋巴细胞和单核细胞表面表达较弱,但经刺激后可诱导到细胞表面表达。能够诱导APP膜表达的细胞激活剂包括有丝分裂凝集素、钙离子载体、磷酸酶抑制剂以及B细胞和T细胞中的抗mu-chain或抗cd3抗体。有趣的是,磷酸酯能诱导单核细胞APP膜表达,但不能诱导淋巴样细胞APP膜表达。与淋巴细胞和单核细胞相比,粒细胞从未表达细胞表面或细胞质APP,即使在激活后也是如此。膜APP对淋巴细胞激活信号(包括B细胞和T细胞抗原受体的抗体)的响应诱导,提出了APP可能在免疫系统中发挥细胞表面受体作用的可能性。
A4-amyloid is the major component pc senile plaques and neurofibrillary tangles found in the brain of patients suffering Alzheimer's disease. This 39-42 amino acid peptide is derived from a larger precursor protein (APP). Since APP gene encodes for a putative memebrane protein, the study of APP expression at the cell surface may provide useful data for understanding its physiological function. In this report, we present data on APP expression, that was detected by APP specific mAbs in cells of the hematopoietic system. APP was weakly expressed on the cell surface of resting human lymphocytes and monocytes, but it could be induced to the surface of those cells upon stimulation. The cell activators capable of inducing APP membrane expression comprehended mitogenic lectins, calcium ionophores, phosphatase inhibitors, and anti mu-chain or anti-CD3 antibodies in B and T cells, respectively. Interestingly, phorbol esters were able to induce APP membrane expression in monocytic, but not in lymphoid cells. In contrast to lymphocytes and monocytes, granulocytes never expressed cell surface or cytoplasmic APP, even after the activation. The induction of membrane APP in response to lymphocyte activation signals, including antibodies to the antigen receptor of B and T cells, raises the possibility that APP might play the role of a cell surface receptor in the immune system.