Modulation of Neutrophil Functions by Neurotransmitters Implicated in Stress

<p>Stress has long been implicated in immune modulation. People under chronic stress have no change in the circulating basal levels of catecholamines while plasma levels of neuropeptide Y (NPY) are significantly increased. Sympathetic nerve fibers with NPY have been found to innervate immune organs. It was hypothesized that NPY might be a mediator in immune modulation in people under chronic stress. Human neutrophils were used as a model to study the effects of NPY alone or together with norepinephrine on the immune system. We now report that NPY modulates oxidative burst (OB) triggered by zymosan in human neutrophils while it has no effects on the phagocytosis process. NPY did not trigger but did enhance OB in a time and dose-dependent fashion. The reaction was specific since non-specific peptides did not produce any significant effects, and anti-NPY antibody essentially neutralized this enhancement while antibody which was non-specific for NPY did not block the modulation. The enhancement of OB was not due to a general activation of metabolism of the neutrophils since the cytosolic non-specific esterases (measured by calcein-AM), the mitochondrial dehydrogenases (measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide), and oxygen consumption were not affected by NPY. NPY may be an important link in neuro-immune modulation under chronic stress. Modulation of neutrophil OB by NPY is likely to involve an atypical receptor that has not been described in the literature since peptide YY, [Leu³¹,Pro³⁴]NPY, and NPY C-terminal fragment 13-36 induced comparable responses to NPY and none of the known receptor antagonists could block the NPY-induced modulation. Synthesis of macromolecules is probably not involved in the modulation process since cycloheximide (a protein synthesis inhibitor) and 5,6-dichlorobenzimidazole riboside (an RNA synthesis inhibitor) did not block the modulation. NPY enhanced the OB triggered by zymosan and N-formyl-Met-Leu-Phe, but not by phorbal myristate acetate. This indicated that the modulation does not involve protein kinase C or NADPH-oxidase. Compound R24571 (a calmodulin inhibitor) did not affect the oxidative burst process or inhibit the NPY modulation, indicating that Ca⁺⁺/calmodulin dependent enzymes are not involved in the modulation process.</p>

Name thesis:degree_name

Doctor of Philosophy (PhD)

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Microbiology

Year

1995

Author dc:creator

• Wan, Chok Ping

Contributors dc:contributor

• Benjamin H. S. Lau
• Christopher D. Cain
• Peter Yu-An Chang
• Lora Green
• Daila Gridley
• George Javor

• Microbiology
• Neurosciences
• Neurotransmitters; Stress; Neuropeptide Y; Signal Transduction

Statement dc:rights

• This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Language dc:language

English

Repository record dc:identifier

https://scholarsrepository.llu.edu/etd/843

OAI identifier oai:identifier

oai:scholarsrepository.llu.edu:etd-1922