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

Abstract

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.

Age-related differences in immune dynamics during SARS-CoV-2 infection in rhesus macaques

“…However, concentrations of other cytokines associated with chronic inflammation, like TNF-α (p = 0.70) and IL-1RA (p = 0.88), were not increased (Fig. S1) 16, 17 . Although not as strongly differentiated, IL-5 (p = 0.12) and IL-8 (p = 0.07) were detected at lower concentrations in the older compared to younger animals (Fig.…”

Simultaneous Measurement of Changes in Neutrophil Granulocyte Membrane Potential, Intracellular pH, and Cell Size by Multiparametric Flow Cytometry

“…Neutrophil activation by the above-mentioned chemoattractants typically induces a certain response pattern, including depolarization of the membrane potential (MP), alkalization of the intracellular pH (pH i ), and a change in cellular shape as reported by our group [4,[14][15][16][17][18] and many others [19][20][21][22][23][24]. These distinct alterations are closely associated with crucial neutrophil functions.…”

Once Upon a Time

“…The third article, written by Bernhard et al [11], deals with IL-8 [11]. The authors found that IL-8 elicits rapid physiological changes in neutrophils that are altered by inflammatory conditions such as fMLP or LPS [11].…”

“…The third article, written by Bernhard et al [11], deals with IL-8 [11]. The authors found that IL-8 elicits rapid physiological changes in neutrophils that are altered by inflammatory conditions such as fMLP or LPS [11]. Notably, IL-8 levels are increased for instance under inflammatory conditions such as trauma [14] and thus the study of this critical chemotactic factor will be of help to understand how inflammatory responses can be modulated.…”

“…Notably, IL-8 levels are increased for instance under inflammatory conditions such as trauma [14] and thus the study of this critical chemotactic factor will be of help to understand how inflammatory responses can be modulated. To this end, the authors report that ion channels and transporters play an important role in these processes which allowed them conclude that targeting these proteins can be used for diagnostic purposes [11].…”