Institute for Medical Microbiology and Hygiene, University of Lübeck, Lübeck, Germany.
J Immunol. 2010 Jan 1;184(1):391-400. doi: 10.4049/jimmunol.0900564. Epub 2009 Nov 30.
Neutrophil granulocytes are rapidly recruited from the bloodstream to the site of acute inflammation where they die in large numbers. Because release of toxic substances from dead neutrophils can propagate the inflammatory response leading to tissue destruction, clearance of dying inflammatory neutrophils has a critical function in the resolution of the inflammatory response. Apoptotic neutrophils are phagocytosed primarily by macrophages, provided these cells are present in adequate numbers. However, macrophages are rare at sites of acute inflammation, whereas the number of neutrophils can be extremely high. In the current study, in vitro experiments with human neutrophils were carried out to investigate whether neutrophils can ingest apoptotic neutrophils. We show that naïve granulocytes isolated from venous blood have a limited capacity to phagocytose apoptotic cells. However, exposure to activating stimuli such as LPS, GM-CSF and/or IFN-gamma results in enhanced phagocytosis of apoptotic cells. The efficient uptake of apoptotic cells by neutrophils was found to depend on the presence of heat labile serum factors. Importantly, the contact to or uptake of apoptotic cells inhibited neutrophil functions such as respiratory burst and the release of the proinflammatory cytokines TNF-alpha and interferon-inducible protein-10. Contact to apoptotic cells, however, induced the secretion of IL-8 and growth-related oncogene-alpha, which was independent of NF-kappaB and p38 MAPK but involved C5a and the ERK1/2 pathway. The data suggest that activated neutrophils participate in the clearance of apoptotic cells. In addition, because apoptotic cells inhibit proinflammatory functions of neutrophils, uptake of apoptotic cells by neutrophils contributes to the resolution of inflammation.
中性粒细胞从血液中迅速募集到急性炎症部位，大量死亡。由于死亡的中性粒细胞释放的毒性物质可以促进炎症反应，导致组织破坏，因此清除死亡的炎症中性粒细胞在炎症反应的消退中具有关键作用。凋亡的中性粒细胞主要被巨噬细胞吞噬，如果这些细胞数量足够。然而，在急性炎症部位巨噬细胞很少，而中性粒细胞的数量可能非常高。在本研究中，进行了体外实验，以研究人类中性粒细胞是否可以吞噬凋亡的中性粒细胞。我们表明，从静脉血中分离出的幼稚粒细胞吞噬凋亡细胞的能力有限。然而，暴露于激活剂刺激物，如 LPS、GM-CSF 和/或 IFN-γ，会导致对凋亡细胞的吞噬作用增强。中性粒细胞有效摄取凋亡细胞的能力取决于热不稳定血清因子的存在。重要的是，凋亡细胞与中性粒细胞的接触或摄取会抑制中性粒细胞的功能，如呼吸爆发和促炎细胞因子 TNF-α和干扰素诱导蛋白-10 的释放。然而，与凋亡细胞接触会诱导 IL-8 和生长相关癌基因-α的分泌，这与 NF-κB 和 p38 MAPK 无关，但涉及 C5a 和 ERK1/2 途径。这些数据表明，活化的中性粒细胞参与清除凋亡细胞。此外，由于凋亡细胞抑制中性粒细胞的促炎功能，因此中性粒细胞摄取凋亡细胞有助于炎症的消退。
