Chemotactic agents induce IL‐6Rα shedding from polymorphonuclear cells: involvement of a metalloproteinase of the TNF‐α‐converting enzyme (TACE) type

V Marin, F Montero‐Julian, S Grès… - European journal of …, 2002 - Wiley Online Library
V Marin, F Montero‐Julian, S Grès, P Bongrand, C Farnarier, G Kaplanski
European journal of immunology, 2002Wiley Online Library
Abstract Interleukin (IL)‐6 transsignaling plays a pivotal role in the shift from neutrophil to
monocyte recruitment at the inflammatory site. Release of neutrophil IL‐6 receptor‐α (IL‐
6Rα, CD126) in its soluble form is a key step of IL‐6 transsignaling, however, its
physiological inducers are poorly known. Here, we observed that the neutrophil
chemoattractants IL‐8, C5a complement fraction, platelet activating factor, leukotriene B4
and N‐formyl‐methionyl‐leucyl‐phenylalanine rapidly decreased IL‐6Rα membrane …
Abstract
Interleukin (IL)‐6 transsignaling plays a pivotal role in the shift from neutrophil to monocyte recruitment at the inflammatory site. Release of neutrophil IL‐6 receptor‐α (IL‐6Rα, CD126) in its soluble form is a key step of IL‐6 transsignaling, however, its physiological inducers are poorly known. Here, we observed that the neutrophil chemoattractants IL‐8, C5a complement fraction, platelet activating factor, leukotriene B4 and N‐formyl‐methionyl‐leucyl‐phenylalanine rapidly decreased IL‐6Rα membrane expression and increased soluble IL‐6Rα concentrations in the neutrophil supernatants, consistent with a shedding process. IL‐6Rα shedding involved a TNF‐α‐converting enzyme‐type metalloproteinase since it was partly decreased in the presence of a specific inhibitor, but not cathepsin G since PMSF or α1 antichymotrypsin had no effect. Neutrophil IL‐6Rα shedding may be a common feature of neutrophilic infiltrates in various inflammatory situations, allowing IL‐6 transsignaling, decreasing neutrophil infiltration and in the meantime favoring monocyte recruitment, thus the initiation of an immune response and subsequently the resolution of inflammation.
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