Department of Microbiology and Immunology, McGill University, Montreal, H3A 2B4, Canada.
McGill Research Centre for Complex Traits , McGill University, Montreal, H3G 0B1, Canada.
J Cell Sci. 2023 Jun 1;136(11). doi: 10.1242/jcs.260768. Epub 2023 Jun 8.
Neutrophils are among the fastest-moving immune cells. Their speed is critical to their function as 'first responder' cells at sites of damage or infection, and it has been postulated that the unique segmented nucleus of neutrophils functions to assist their rapid migration. Here, we tested this hypothesis by imaging primary human neutrophils traversing narrow channels in custom-designed microfluidic devices. Individuals were given an intravenous low dose of endotoxin to elicit recruitment of neutrophils into the blood with a high diversity of nuclear phenotypes, ranging from hypo- to hyper-segmented. Both by cell sorting of neutrophils from the blood using markers that correlate with lobularity and by directly quantifying the migration of neutrophils with distinct lobe numbers, we found that neutrophils with one or two nuclear lobes were significantly slower to traverse narrower channels, compared to neutrophils with more than two nuclear lobes. Thus, our data show that nuclear segmentation in primary human neutrophils provides a speed advantage during migration through confined spaces.
中性粒细胞是移动速度最快的免疫细胞之一。它们的速度对于作为“第一反应”细胞在损伤或感染部位发挥作用至关重要，有人假设中性粒细胞独特的分段核有助于其快速迁移。在这里，我们通过在定制设计的微流控设备中成像穿过狭窄通道的原代人中性粒细胞来测试这一假设。通过静脉内给予低剂量内毒素，将个体的中性粒细胞募集到血液中，其核表型具有高度多样性，从低到高度分段。通过使用与叶状相关的标记物从血液中对中性粒细胞进行细胞分选，以及直接定量具有不同叶数的中性粒细胞的迁移，我们发现具有一个或两个核叶的中性粒细胞穿过较窄通道的速度明显较慢，与具有两个以上核叶的中性粒细胞相比。因此，我们的数据表明，原发性人中性粒细胞中的核分段在通过受限空间迁移时提供了速度优势。
