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Blood, Vol. 92 No. 12 (December 15), 1998:
pp. 4828-4835
Interleukin-15 (IL-15) Induces NF- B Activation and IL-8
Production in Human Neutrophils
Patrick P. McDonald,
Maria Pia Russo,
Silvano Ferrini, and
Marco
A. Cassatella
From the Department of General Pathology, University of Verona,
Verona, Italy; and the Centro di Biotecnologie Avanzate, Istituto
Nazionale per la Ricerca sul Cancro, Genova, Italy.
Interleukin-2 (IL-2) and IL-15 exert similar biological actions,
which largely reflect the fact that their receptors share common  and  subunits; in contrast, distinct  subunits are required for
high-affinity binding of either cytokine to a heterotrimeric receptor
complex. Human neutrophils are known to express both the and subunits of the IL-2/IL-15 receptor complex, and we now report that
they also constitutively express messenger RNA transcripts encoding the
IL-15 receptor chain, suggesting that they possess functional,
heterotrimeric IL-15 receptors. Accordingly, we show that in
neutrophils, IL-15 elicits several functional responses. In particular,
neutrophils synthesize and release IL-8 in response to IL-15, but not
to IL-2. Moreover, a nuclear factor- B (NF-B) DNA-binding activity
was enhanced in nuclear extracts of IL-15-treated neutrophils, which
could be supershifted by antibodies to p50 or RelA. Again, no
detectable effect of IL-2 was observed on this response. In peripheral
blood lymphocytes (PBL), however, both IL-2 and IL-15 were potent
inducers of NF-B activation. Conversely, neither IL-15 nor IL-2
elicited the formation of activator protein-1 (AP-1) DNA-binding
complexes in neutrophils, even though both cytokines were found to
activate these DNA-binding activities in PBL. Collectively, these
observations establish neutrophils as a useful cellular model to
discriminate between the actions of IL-15 and IL-2. More importantly,
this is the first demonstration that IL-15 has the ability to induce
NF-B and AP-1 activation, which further emphasizes the potential
relevance of this newly discovered cytokine to immune and inflammatory
processes.
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