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Blood, 15 March 2002, Vol. 99, No. 6, pp. 2214-2220
PHAGOCYTES
Human eosinophils produce neurotrophins and secrete nerve growth
factor on immunologic stimuli
Hitoshi Kobayashi,
Gerald
J. Gleich,
Joseph H. Butterfield, and
Hirohito Kita
From the Department of Medicine, Mayo Clinic,
Rochester, MN.
Neurotrophins, such as nerve growth factor (NGF) and
neurotrophin-3 (NT-3), are essential for development, function, and
survival of peripheral sympathetic and sensory neurons. Most
eosinophilic leukocytes in the human body are localized in mucosal
tissues; however, the roles of eosinophils in human diseases are not
fully understood. We found that human eosinophils constitutively
express messenger RNA for NGF and NT-3, synthesize and store these
proteins intracellularly, and continuously replenish them. Incubation
of eosinophils with a transcription inhibitor, actinomycin D, for 8 hours completely depletes intracellular NGF and NT-3. New synthesis of
NGF is enhanced by Fc-receptor-mediated stimuli, such as
immunoglobulin (Ig)A and IgG immune complexes; in contrast, production
of NT-3 is not affected by these stimuli. Notably, supernatants of
eosinophils stimulated with IgA immune complex and interleukin 5 promote neurite extension of the PC-12 pheochromocytoma cell line; this
effect is abolished by pretreatment of the supernatants with
anti-NGF-neutralizing antibody. By enzyme-linked immunosorbent assay,
substantial amounts of NGF protein are also detected in the
supernatants of stimulated eosinophils. Furthermore, in patients with
seasonal allergic rhinitis, the concentrations of NGF in nasal
secretions correlate with the magnitudes of eosinophilic inflammation
in the airway, suggesting a potential clinical implication of
eosinophil NGF. Our observations propose a new pathologic mechanism by
which eosinophils may contribute to enhanced neurologic responses in
patients with allergic diseases and other eosinophilic disorders.
Alternatively, eosinophils may play important roles in maintenance and
restoration of homeostatic functions of mucosal tissues through the
pleitropic activities of NGF.

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