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.