Platelet-derived microparticles stimulate proliferation, survival, adhesion, and chemotaxis of hematopoietic cells
Platelet-derived microparticles stimulate proliferation, survival, adhesion, and chemotaxis of hematopoietic cells
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DOI：
10.1016/s0301-472x(02)00791-9
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发表时间：
2002-05-01
影响因子：
2.6
通讯作者：
Ratajczak, MZ
中科院分区：
文献类型：
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作者：
Baj-Krzyworzeka, M;Majka, M;Ratajczak, MZ
目标。外周血小板源微粒(PMPs)在血液中循环，可直接与靶细胞相互作用，影响其各种生物学功能。为了研究人PMPs对造血的影响，我们首先对PMPs的各种表面分子的表达进行了表型鉴定，然后研究了正常干/祖细胞(CD34(+))和更分化的前体细胞以及几种白血病细胞株对PMPs的各种生物学反应。我们发现，除了血小板-内皮附着受体(CD41、CD61和CD62)外，PMPS还表达G蛋白偶联的七种跨膜受体，如CXCR4和PAR-1；细胞因子受体包括TNF-RI、TNF-RII和CD95；以及配体CD40L和PF-4。此外，我们发现PMPs可以将这些受体中的几种转移到细胞膜或正常细胞和恶性肿瘤细胞上，观察到PMPs：1)化学吸引这些细胞，2)增加它们的黏附、增殖和存活，3)在这些细胞中激活各种细胞内信号转导通路，包括MAPK p42/44、PI-3K-AKT和STAT蛋白。热灭活或胰酶消化只能部分降低PMPs的生物学活性，说明PMPs的生物活性除与蛋白质组分有关外，还与脂类组分有关。我们的结论是，PMPs调节生物功能或造血细胞，并假设它们在造血过程中的细胞间串扰中发挥着重要但尚未完全了解的作用。然而，还需要进一步的研究来确定具有特定生物学效应的PMP成分。(C)2002年国际实验血液学学会。爱思唯尔科学公司出版。
Objective. Peripheral blood platelet-derived microparticles (PMPs) circulate in blood and may interact directly with target cells affecting their various biological functions.Methods. To investigate the effect of human PMPs on hematopoiesis, we first phenotyped them for expression of various surface molecules and subsequently studied various biological responses of normal stem/progenitor (CD34(+)) and more differentiated precursor cells as well as several leukemic cell lines to PMPs.Results. We found that, in addition to platelet-endothelium attachment receptors (CD41, CD61 and CD62), PMPs express G-protein-coupled seven transmembrane-span receptors such as CXCR4 and PAR-1; cytokine receptors including TNF-RI, TNF-RII, and CD95; and ligands such as CD40L and PF-4. Moreover, we found that several of these receptors could be transferred by PMPs to the membranes or normal as well as malignant cells and observed that PMPs: 1) chemoattract these cells, 2) increase their adhesion, proliferation, and survival, and 3) activate in these cells various intracellular signaling cascades including MAPK p42/44, PI-3K-AKT, and STAT proteins. The biological effects of PMPs were only partly reduced by heat inactivation or trypsin digest, indicating that, in addition to the protein components of PMPs, lipid components are also responsible for their biological activity.Conclusions. We conclude that PMPs modulate biological functions or hematopoietic cells and postulate that they play an important but as yet not fully understood role in intercellular cross-talk in hematopoiesis. Further studies, however, are needed to identify the PMP components that exert specific biological effects. (C) 2002 International Society for Experimental Hematology. Published by Elsevier Science Inc.