Medizinische Klinik III, Eberhard Karls Universität Tübingen, Germany.
Semin Thromb Hemost. 2010 Mar;36(2):157-62. doi: 10.1055/s-0030-1251499. Epub 2010 Apr 22.
CD34 (+) progenitor cells are a promising source of regeneration in atherosclerosis or ischemic heart disease. However, as recently published, CD34(+) progenitor cells have the potential to differentiate not only into endothelial cells but also into foam cells upon interaction with platelets. The mechanism of platelet-induced differentiation of progenitor cells into foam cells is as yet unclear. In the present study we investigated the role of scavenger receptor (SR)-A and CD36 in platelet-induced foam cell formation. Human CD34(+) progenitor cells were freshly derived from human umbilical veins and were co-incubated with platelets (2 x 10(8)/mL) up to 14 days resulting in large lipid-laden foam cells. Developing macrophages expressed SR-A, CD36, and Lox-1 as measured by fluorescent-activated cell sorting analysis. The presence of a blocking anti-CD36 or anti-SR-A antibody nearly abrogated foam cell formation, whereas anti-Lox-1 did not affect foam cell formation. Consistently blocking either anti-CD36 or anti-SR-A antibody significantly reduced the phagocytosis of lipid-laden platelets by macrophages. We conclude that CD36 and SR-A play an important role in platelet-induced foam cell formation from CD34(+) progenitor cells and thus represent a promising target to inhibit platelet-induced foam cell formation.
CD34(+) 祖细胞是动脉粥样硬化或缺血性心脏病再生的有前途的来源。然而，正如最近发表的那样，CD34(+) 祖细胞不仅有潜力分化为内皮细胞，而且在与血小板相互作用时还具有分化为泡沫细胞的潜力。血小板诱导祖细胞分化为泡沫细胞的机制尚不清楚。在本研究中，我们研究了清道夫受体 (SR)-A 和 CD36 在血小板诱导泡沫细胞形成中的作用。人脐静脉来源的新鲜人 CD34(+) 祖细胞与血小板 (2 x 10(8)/mL) 共孵育长达 14 天，导致大脂质负荷的泡沫细胞。通过荧光激活细胞分选分析测量，发育中的巨噬细胞表达 SR-A、CD36 和 Lox-1。用阻断抗 CD36 或抗 SR-A 抗体存在几乎消除了泡沫细胞的形成，而抗 Lox-1 则不影响泡沫细胞的形成。一致地阻断抗 CD36 或抗 SR-A 抗体显著减少了巨噬细胞对富含脂质的血小板的吞噬作用。我们得出结论，CD36 和 SR-A 在 CD34(+) 祖细胞中血小板诱导的泡沫细胞形成中起重要作用，因此代表了抑制血小板诱导的泡沫细胞形成的有前途的靶点。
