未成熟髓系树突状细胞从预先形成的聚集物中捕获并清除激活的血小板。

Immature myeloid dendritic cells capture and remove activated platelets from preformed aggregates.

机构信息

UMR-S949 INSERM, France.

出版信息

J Thromb Haemost. 2010 Oct;8(10):2262-72. doi: 10.1111/j.1538-7836.2010.03983.x.

Abstract

BACKGROUND

Immature dendritic cells (DCs) patrol the circulation, where they can uptake antigens. It has been reported that mature monocyte-derived DCs have the ability to interact with an activated platelet monolayer under high shear conditions (1500s(-1) ).

OBJECTIVES

In this study, we investigated whether platelets can recruit immature myeloid DCs (CD1c(+) ) directly isolated from blood (BDCs) and if so, which receptors are involved.

RESULTS

Using flow cytometry and electron microscopy, we showed that BDCs interact with activated but not resting platelets in suspension. Interaction was also observed after perfusing BDCs under low flow conditions (150 s(-1) ) through collagen-coated microcapillaries in which platelets had adhered and formed aggregates. No such interaction could be detected at higher shear rates. Whereas initial transient attachment required the exposure of P-selectin on activated platelets and PSGL-1 on BDCs, subsequent stationary adhesion was dependent on α(IIb) β(3) and α(M) β(2) integrins on platelets and BDCs, respectively. Moreover, during their transient interaction, BDCs preferentially removed platelets located at the outer margin of the thrombus in a P-selectin- and integrin-dependent manner.

CONCLUSION

This study provides evidence for an interaction between activated platelets and immature myeloid DCs only under low shear conditions. This could be of importance for BDC maturation and antigen uptake during normal hemostasis or in the context of atherothrombosis at sites of reduced blood flow.

摘要

背景

不成熟的树突状细胞(DC)在循环中巡逻,在那里它们可以摄取抗原。据报道,成熟的单核细胞衍生的 DC 具有在高剪切条件(1500s(-1) )下与激活的血小板单层相互作用的能力。

目的

在这项研究中,我们研究了血小板是否可以直接招募从血液中分离出来的不成熟髓样 DC(CD1c(+) ),如果可以,涉及哪些受体。

结果

使用流式细胞术和电子显微镜,我们表明 BDC 在悬浮液中与激活的血小板而不是静止的血小板相互作用。在通过胶原涂覆的微毛细管以低流速(150s(-1) )灌注 BDC 后,也观察到了相互作用,其中血小板已粘附并形成聚集体。在更高的剪切速率下则无法检测到这种相互作用。尽管最初的瞬时附着需要激活血小板上的 P-选择素和 BDC 上的 PSGL-1 的暴露,但随后的固定附着分别依赖于血小板和 BDC 上的 α(IIb)β(3) 和 α(M)β(2)整合素。此外,在它们的短暂相互作用中,BDC 以依赖于 P-选择素和整合素的方式优先去除血栓外边缘处的血小板。

结论

这项研究为激活的血小板和不成熟的髓样 DC 之间的相互作用提供了证据,这种相互作用仅在低剪切条件下发生。这对于正常止血期间的 BDC 成熟和抗原摄取,或在血流减少部位的动脉血栓形成中可能具有重要意义。

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