Differential effects of interleukin-15 (IL-15) and IL-2 on human neutrophils: modulation of phagocytosis, cytoskeleton rearrangement, gene expression, and apoptosis by IL-15

Abstract

Human neutrophils have been shown recently to express both the beta and the gamma chains of the interleukin-2 receptor (IL-2R). IL-15, a cytokine that has recently been cloned and characterized, was found to share many of the biological functions of IL-2 and is known to mediate signals through IL-2R beta and IL-2R gamma. In recent studies, we observed that IL-2 exerts few effects on various neutrophil functions, but information on IL-15-neutrophil interactions is lacking. In this study, we observed that IL-15, in contrast to IL-2, induces important morphological cell shape changes that are typical of activated neutrophils. Furthermore, phagocytosis of opsonized sheep red blood cells was significantly increased by IL-15 but not by IL-2. However, similar to IL-2, IL-15 did not modulate the oxidative burst response. Furthermore, we observed that de novo RNA synthesis is increased in neutrophils by IL-15 along with de novo protein synthesis, whereas no significant effect of IL-2 was noted. Among the different proteins that were found to be upregulated by IL-15, one was identified by microsequencing as the cytoskeletal protein actin. Finally, we found that IL-15 delays apoptosis of neutrophils more efficiently than IL-2 when evaluated by both microscopic observations and flow cytometry procedures. Furthermore, this phenomenon was dose-dependent (10 to 500 ng/mL), and, at 500 ng/mL, IL-15 delayed apoptosis as strongly as granulocyte-macrophage colony-stimulating factor. This study is the first to show that IL-15 is a significant neutrophil agonist. Moreover, in view of the differential effects of IL-15 and IL-2 on this cell type, our results support the existence of a specific IL-15R component(s) on human neutrophils.

Virus-Infected Alveolar Epithelial Cells Direct Neutrophil Chemotaxis and Inhibit Their Apoptosis

“…In addition to CXC chemokines, PMN apoptosis is also inhibited by cytokines, including GM-CSF, G-CSF, IL-1b, IL-6, IFN-g, TNF-a, and IL-15 (35,39,40). In contrast, other proinflammatory cytokines, such as TNF-a and IL-6, significantly induce PMN apoptosis (41)(42)(43).…”

Anti-Inflammatory Role of Interleukin-15 in Crohnʼs Disease

“…[24][25][26][27] Notably, IL-15 is recognized for its antiapoptotic effects on T CD8 + memory cells and inhibition of the IL-2-mediated activation-induced cell death. [17][18][19][20]47 It thus seems unlikely that the coincident stimulation with IL-15 would lead to apoptosis of activated cells.…”

Interaction between silver nanoparticles of 20 nm (AgNP20) and human neutrophils: induction of apoptosis and inhibition of de novo protein synthesis by AgNP20 aggregates

“…Silver Nanoparticles of 20 nm Increased the Neutrophil Cell Size Next, as a marker of PMN activation, cell shape changes were monitored by cytology after AgNP 20 treatment, as done routinely in our laboratory (Girard et al, 1996;Goncalves et al, 2010). As illustrated in Fig.…”