Phagocytosis by Thrombocytes is a Conserved Innate Immune Mechanism in Lower Vertebrates.

Phagocytosis by Thrombocytes is a Conserved Innate Immune Mechanism in Lower Vertebrates.
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DOI:
10.3389/fimmu.2014.00445
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发表时间:
2014
影响因子:
7.3
通讯作者:
Nakao M
Nakao M
中科院分区:
医学2区
文献类型:
--
作者:
Nagasawa T;Nakayasu C;Rieger AM;Barreda DR;Somamoto T;Nakao M

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血小板,非哺乳动物脊椎动物的有核止血血细胞,被认为是无核哺乳动物血小板的功能等同物。其他免疫功能,包括吞噬功能,也被认为对血小板有作用,但迄今为止还没有提供结论性的分子或细胞实验证据,证明它们可能摄入和清除浸润的微生物。在本研究中,我们利用硬骨鱼和两栖动物模型证明了低等脊椎动物中血小板的活性吞噬能力。在体外,普通鲤鱼血小板能够摄取活细菌和直径0.5-3 μm的乳胶珠并杀死细菌。在体内,我们发现在普通鲤鱼外周血白细胞池中,血小板几乎占吞噬细胞总数的一半。血清调理进一步提高了吞噬效率。颗粒内化导致吞噬溶酶体融合并杀死内化的细菌,表明颗粒具有强大的消除微生物的能力。我们发现这种强大的吞噬活性在硬骨鱼(palichthys olivaceus)和两栖动物(Xenopus laevis)模型中是共享的,这意味着它在整个低等脊椎动物谱系中都是守恒的。我们的研究结果为血小板在免疫和体内平衡反应中的双重性质提供了新的见解,并进一步提供了基于保守和退化功能的哺乳动物血小板潜在免疫功能的更深入理解。
Thrombocytes, nucleated hemostatic blood cells of non-mammalian vertebrates, are regarded as the functional equivalent of anucleated mammalian platelets. Additional immune functions, including phagocytosis, have also been suggested for thrombocytes, but no conclusive molecular or cellular experimental evidence for their potential ingestion and clearance of infiltrating microbes has been provided till date. In the present study, we demonstrate the active phagocytic ability of thrombocytes in lower vertebrates using teleost fishes and amphibian models. Ex vivo, common carp thrombocytes were able to ingest live bacteria as well as latex beads (0.5–3 μm in diameter) and kill the bacteria. In vivo, we found that thrombocytes represented nearly half of the phagocyte population in the common carp total peripheral blood leukocyte pool. Phagocytosis efficiency was further enhanced by serum opsonization. Particle internalization led to phagolysosome fusion and killing of internalized bacteria, pointing to a robust ability for microbe elimination. We find that this potent phagocytic activity is shared across teleost (Paralichthys olivaceus) and amphibian (Xenopus laevis) models examined, implying its conservation throughout the lower vertebrate lineage. Our results provide novel insights into the dual nature of thrombocytes in the immune and homeostatic response and further provide a deeper understanding of the potential immune function of mammalian platelets based on the conserved and vestigial functions.
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