Gasser Olivier, Schifferli Jürg A
Immunonephrology Laboratory, Department of Research, University Hospital Basel, Hebelstrasse 20, 4031 Basel, Switzerland.
Blood. 2004 Oct 15;104(8):2543-8. doi: 10.1182/blood-2004-01-0361. Epub 2004 Jun 22.
On activation, human neutrophils release microparticles, called ectosomes, directly from the cell surface membrane. Microparticles from platelets, endothelial cells, and monocytes were reported to support coagulation or to modulate vascular homeostasis by activating monocytes as well as endothelial cells. We find that neutrophil ectosomes have no proinflammatory activity on human macrophages as assessed by the release of interleukin 8 (IL-8) and tumor necrosis factor alpha (TNFalpha). On the contrary, ectosomes increase the release of transforming growth factor beta1 (TGFbeta1), suggesting that ectosomes down-modulate cellular activation in macrophages. Polymorphonuclear neutrophil (PMN) ectosomes are able to block inflammatory response of macrophages to zymosan and lipopolysaccharide (LPS). We show that an early-phase TGFbeta1 secretion and the exposure of phosphatidylserine on the surface of ectosomes independently contribute to this effect. Ectosome-cell contact was sufficient for their immunomodulatory function as shown by blocking phagocytosis with cytochalasin D. Thus, neutrophils release potent anti-inflammatory effectors, in the form of ectosomes, at the earliest stage of inflammation, already providing a drive to its resolution.
激活后，人类中性粒细胞会直接从细胞表面膜释放被称为胞外体的微粒。据报道，来自血小板、内皮细胞和单核细胞的微粒可通过激活单核细胞以及内皮细胞来支持凝血或调节血管稳态。我们发现，通过白细胞介素8（IL-8）和肿瘤坏死因子α（TNFα）的释放来评估，中性粒细胞胞外体对人类巨噬细胞没有促炎活性。相反，胞外体会增加转化生长因子β1（TGFβ1）的释放，这表明胞外体会下调巨噬细胞中的细胞活化。多形核中性粒细胞（PMN）胞外体能够阻断巨噬细胞对酵母聚糖和脂多糖（LPS）的炎症反应。我们表明，早期的TGFβ1分泌以及胞外体表面磷脂酰丝氨酸的暴露独立地促成了这种效应。如用细胞松弛素D阻断吞噬作用所示，胞外体与细胞的接触足以实现其免疫调节功能。因此，中性粒细胞在炎症的最早阶段就以胞外体的形式释放出强效的抗炎效应物，已经为炎症的消退提供了驱动力。
