Activated polymorphonuclear neutrophils disseminate anti-inflammatory microparticles by ectocytosis.
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.
Gasser
Olivier
O
Immunonephrology Laboratory, Department of Research, University Hospital Basel, Hebelstrasse 20, 4031 Basel, Switzerland. olivier.gasser@unibas.ch
Schifferli
Jürg A
JA
D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D015638:Cytochalasin D / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D018613:Microscopy, Confocal; D018375:Neutrophil Activation; D009504:Neutrophils / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects; D010768:Phosphoserine / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000276:immunology; D015054:Zymosan / Q000276:immunology / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D000906:Antibodies; D016207:Cytokines; D008070:Lipopolysaccharides; D016212:Transforming Growth Factor beta; D010768:Phosphoserine; D015638:Cytochalasin D; D015054:Zymosan