Soslau G, Morgan D A, Jaffe J S, Brodsky I, Wang Y
Department of Biochemistry/IMS, Allegheny University of the Health Sciences, Philadelphia, PA 19102, USA.
Cytokine. 1997 Jun;9(6):405-11. doi: 10.1006/cyto.1996.0182.
Platelet formation and function are regulated, in vivo, to varying degrees by cytokines in the micro-environment. While white blood cells are the major source of cytokines within the cardiovascular system, the question addressed in this study was whether platelets and the platelet precursor, the megakaryocyte, may also serve as a source of cytokines. Cytokines produced by or carried within platelets could be released at sites of vascular injury and participate in wound healing. Platelets and a human megakaryocyte-like cell line, HU3, were found to express message for interleukin 7 (IL-7), stem cell factor (SCF), transforming growth factor beta (TGF-beta), cMpl, the IgE receptor subunits Fc epsilon RI alpha gamma and the transcription factor, NF-E2. Other cytokines expressed in HU3 cells but not in platelets included IL-1 beta, IL-6, IL-10, IL-13, TNF-alpha and the FC epsilon RI beta subunit. The HU3 cell line seemed to be further along the maturation/differentiation pathway to platelet formation than a second blood derived bipotential cell line, MB02. The MB02 cell line did not express IL-6, IL-10, SCF, TNF-omega nor cMpl. Furthermore, culturing the HU3 cells in TPO appeared to repress expression of Fc epsilon RI beta directing the cell closer to the platelet phenotype. In light of the presence of cytokine expression in platelets/megakaryocytes, agonist-induced platelet aggregation was measured in the presence of added cytokines as a means to evaluate potential cytokine modulation of platelet function. Collagen-induced aggregations were significantly enhanced by IL-6, SCF and TPO. Other cytokines tested significantly stimulated the thrombin receptor activating peptide, SFLLRNP-, U46619- and ADP-induced platelet aggregations with TPO being the most consistent activator. It is possible that cytokines released from platelets act in concert with cytokines released from other cellular sources to modulate haemostasis and thrombosis differentially depending upon the site of injury.
在体内，血小板的形成和功能在不同程度上受到微环境中细胞因子的调节。虽然白细胞是心血管系统中细胞因子的主要来源，但本研究探讨的问题是血小板及其前体巨核细胞是否也可作为细胞因子的来源。血小板产生或携带的细胞因子可在血管损伤部位释放，并参与伤口愈合。研究发现血小板和一种人巨核细胞样细胞系HU3表达白细胞介素7（IL-7）、干细胞因子（SCF）、转化生长因子β（TGF-β）、cMpl、IgE受体亚基FcεRIαγ以及转录因子NF-E2的信息。HU3细胞中表达但血小板中未表达的其他细胞因子包括IL-1β、IL-6、IL-10、IL-13、TNF-α和FcεRIβ亚基。与另一种源自血液的双能细胞系MB02相比，HU3细胞系似乎在向血小板形成的成熟/分化途径上更进一步。MB02细胞系不表达IL-6、IL-10、SCF、TNF-ω和cMpl。此外，在血小板生成素（TPO）中培养HU3细胞似乎会抑制FcεRIβ的表达，使细胞更接近血小板表型。鉴于血小板/巨核细胞中存在细胞因子表达，在添加细胞因子的情况下测量激动剂诱导的血小板聚集，作为评估细胞因子对血小板功能潜在调节作用的一种手段。IL-6、SCF和TPO显著增强了胶原诱导的聚集。测试的其他细胞因子显著刺激了凝血酶受体激活肽、SFLLRNP-、U46619-和ADP诱导的血小板聚集，其中TPO是最一致的激活剂。血小板释放的细胞因子可能与其他细胞来源释放的细胞因子协同作用，根据损伤部位的不同，差异性地调节止血和血栓形成。
