Division of Neonatology, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Immunity. 2010 Jul 23;33(1):106-17. doi: 10.1016/j.immuni.2010.07.009.
The chemokine sink hypothesis pertaining to erythrocyte Duffy Antigen Receptor for Chemokines (DARC) during inflammation has received considerable attention, but lacks direct in vivo evidence. Here we demonstrate, using mice with a targeted deletion in CXCL5, that CXCL5 bound erythrocyte DARC and impaired its chemokine scavenging in blood. CXCL5 increased the plasma concentrations of CXCL1 and CXCL2 in part through inhibiting chemokine scavenging, impairing chemokine gradients and desensitizing CXCR2, which led to decreased neutrophil influx to the lung, increased lung bacterial burden and mortality in an Escherichia coli pneumonia model. In contrast, CXCL5 exerted a predominant role in mediating neutrophil influx to the lung during inflammation after LPS inhalation. Platelets and lung resident cells were the sources of homeostatic CXCL5 in blood and inflammatory CXCL5 in the lung respectively. This study presents a paradigm whereby platelets and red cells alter chemokine scavenging and neutrophil-chemokine interaction during inflammation.
趋化因子汇假说涉及到红细胞趋化因子受体（DARC）在炎症期间的作用，这一假说受到了广泛关注，但缺乏直接的体内证据。在这里，我们利用 CXCL5 基因敲除小鼠证明，CXCL5 结合红细胞 DARC 并损害其在血液中的趋化因子清除作用。CXCL5 通过抑制趋化因子清除作用，增加了 CXCL1 和 CXCL2 的血浆浓度，损害了趋化因子梯度，并使 CXCR2 脱敏，导致肺内中性粒细胞浸润减少、大肠杆菌肺炎模型中肺内细菌负荷增加和死亡率增加。相比之下，在 LPS 吸入引起的炎症期间，CXCL5 主要介导了中性粒细胞向肺内的浸润。血小板和肺驻留细胞分别是血液中稳态 CXCL5 和肺内炎症性 CXCL5 的来源。本研究提出了一个范例，即血小板和红细胞在炎症期间改变趋化因子清除和中性粒细胞-趋化因子相互作用。
