Interleukin-8 and GROα Prime Human Neutrophils for Superoxide Anion Production and Induce up-Regulation of N-Formyl Peptide Receptors

Abstract

Interleukin-8 (IL-8) and GRO alpha are leukocyte-attracting peptides of the chemokine family. To study the priming potential of these chemokines, we measured superoxide anion production and up-regulation of N-formyl peptide receptors in human neutrophils. IL-8 and GRO alpha themselves did not stimulate production of significant amounts of superoxide anions but potentiated N-formyl peptide-induced superoxide anion production in a concentration-dependent manner. Binding measurements by flow cytometry at 37 degrees C with fluorescein-labeled N-formyl peptide revealed enhanced total N-formyl peptide binding after pretreatment of neutrophils with IL-8 and GRO alpha. Binding measurements performed at 4 degrees C indicated that the chemokines stimulated the up-regulation of N-formyl peptide receptors at the cell surface but did not alter their affinity for the ligand. This study indicates that IL-8 and GRO alpha, in addition to their known chemotactic activity, prime neutrophils for superoxide anion production, presumably by up-regulating the number of receptors for strong superoxide-anion-triggering stimuli.

Effect of Interleukin-8 and Granulocyte Colony-Stimulating Factor on Priming and Activation of Bovine Neutrophils

“…Treatment of bovine neutrophils for 18 h with IL-8 or G-CSF did not directly induce an oxidative burst response. These findings are in agreement with previous reports on the effects of IL-8, where treatment of bovine neutrophils for 30 min with human IL-8 induced chemotaxis and secondary granule secretion but not oxidative burst or primary granule release (11,14,22). Similarly, previous studies did not detect significant differences in oxidative burst between G-CSF-treated and untreated cows (18).…”

Neutrophil infiltration, glial reaction, and neurological disease in transgenic mice expressing the chemokine N51/KC in oligodendrocytes.

“…In pathologic conditions other factors are likely to be necessary to activate fully the neutrophil functions of degranulation, respiratory burst, and cytokine secretion. In this regard, the related human neutrophil chemokines IL-8 and GRO␣ do not stimulate superoxide anion production directly, but up-regulate N-formyl peptide receptors on neutrophils and potentiate superoxide production in response to bacterial components (60).…”

Mechanism of transfusion-related acute lung injury induced by HLA class II antibodies

“…Strong candidates for these effects are IL-8 and GRO-␣, because they have been shown to prime human neutrophils for ROS production 38,39 and to induce the release of secondary granules from neutrophils. 40 LTB 4 is also a main product of activated monocytes and can both recruit and prime neutrophils efficiently.…”

“…31,34 The perfusion of ROS or xanthine/xanthine oxidase (which generates O 2 Ϫ ) into isolated lungs of guinea pigs 35 and rabbits 36,37 resulted in pulmonary edema. Here, we demonstrate in an ex vivo model that monocyte supernatants can precipitate TRALI in the presence, but not in the absence, of neutrophils, indicating that effector substances released from antibody-stimulated monocytes are potent stimulators of neutrophils.Strong candidates for these effects are IL-8 and GRO-␣, because they have been shown to prime human neutrophils for ROS production 38,39 and to induce the release of secondary granules from neutrophils. 40 LTB 4 is also a main product of activated monocytes and can both recruit and prime neutrophils efficiently.…”