Human eosinophils produce neurotrophins and secrete nerve growth factor on immunologic stimuli

Hitoshi Kobayashi, Gerald J. Gleich, Joseph H. Butterfield, Hirohito Kita

Research output: Contribution to journalArticle

136 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2214-2220
Number of pages7
JournalBlood
Volume99
Issue number6
DOIs
StatePublished - Mar 15 2002

Fingerprint

Nerve Growth Factors
Nerve Growth Factor
Eosinophils
Neurotrophin 3
Antigen-Antibody Complex
Immunoglobulin A
Mucous Membrane
Immunosorbents
Seasonal Allergic Rhinitis
Fc Receptors
PC12 Cells
Interleukin-5
Dactinomycin
Sensory Receptor Cells
Neurites
Transcription
Neutralizing Antibodies
Human Body
Nose
Nervous System

ASJC Scopus subject areas

  • Hematology

Cite this

Human eosinophils produce neurotrophins and secrete nerve growth factor on immunologic stimuli. / Kobayashi, Hitoshi; Gleich, Gerald J.; Butterfield, Joseph H.; Kita, Hirohito.

In: Blood, Vol. 99, No. 6, 15.03.2002, p. 2214-2220.

Research output: Contribution to journalArticle

Kobayashi, Hitoshi ; Gleich, Gerald J. ; Butterfield, Joseph H. ; Kita, Hirohito. / Human eosinophils produce neurotrophins and secrete nerve growth factor on immunologic stimuli. In: Blood. 2002 ; Vol. 99, No. 6. pp. 2214-2220.
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