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Bernhard, Stefan; Hug, Stefan; Stratmann, Alexander Elias Paul; Erber, Maike; Vidoni, Laura; Knapp, Christiane Leonie; Thomaß, Bertram Dietrich; Fauler, Michael; Nilsson, Bo; Nilsson Ekdahl, Kristina; Föhr, Karl; Braun, Christian Karl; Wohlgemuth, Lisa; Huber-Lang, Markus; Messerer, David Alexander Christian

Interleukin 8 Elicits Rapid Physiological Changes in Neutrophils That Are Altered by Inflammatory Conditions

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  • Medientyp: E-Artikel
  • Titel: Interleukin 8 Elicits Rapid Physiological Changes in Neutrophils That Are Altered by Inflammatory Conditions
  • Beteiligte: Bernhard, Stefan; Hug, Stefan; Stratmann, Alexander Elias Paul; Erber, Maike; Vidoni, Laura; Knapp, Christiane Leonie; Thomaß, Bertram Dietrich; Fauler, Michael; Nilsson, Bo; Nilsson Ekdahl, Kristina; Föhr, Karl; Braun, Christian Karl; Wohlgemuth, Lisa; Huber-Lang, Markus; Messerer, David Alexander Christian
  • Erschienen: S. Karger AG, 2021
  • Erschienen in: Journal of Innate Immunity, 13 (2021) 4, Seite 225-241
  • Sprache: Englisch
  • DOI: 10.1159/000514885
  • ISSN: 1662-811X; 1662-8128
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: A sufficient response of neutrophil granulocytes stimulated by interleukin (IL)-8 is vital during systemic inflammation, for example, in sepsis or severe trauma. Moreover, IL-8 is clinically used as biomarker of inflammatory processes. However, the effects of IL-8 on cellular key regulators of neutrophil properties such as the intracellular pH (pH<sub>i</sub>) in dependence of ion transport proteins and during inflammation remain to be elucidated. Therefore, we investigated in detail the fundamental changes in pH<sub>i</sub>, cellular shape, and chemotactic activity elicited by IL-8. Using flow cytometric methods, we determined that the IL-8-induced cellular activity was largely dependent on specific ion channels and transporters, such as the sodium-proton exchanger 1 (NHE1) and non-NHE1-dependent sodium flux. Exposing neutrophils in vitro to a proinflammatory micromilieu with N-formyl-Met-Leu-Phe, LPS, or IL-8 resulted in a diminished response regarding the increase in cellular size and pH. The detailed kinetics of the reduced reactivity of the neutrophil granulocytes could be illustrated in a near-real-time flow cytometric measurement. Last, the LPS-mediated impairment of the IL-8-induced response in neutrophils was confirmed in a translational, animal-free human whole blood model. Overall, we provide novel mechanistic insights for the interaction of IL-8 with neutrophil granulocytes and report in detail about its alteration during systemic inflammation.
  • Zugangsstatus: Freier Zugang