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NIH grant 1R16AI200907-01: Exploring Dopamine's Influence on Human Neutrophil Inflammatory Responses
Institute: {'code': 'AI', 'abbreviation': 'NIAID', 'name': 'National Institute of Allergy and Infectious Diseases', 'admin_org_id': '12500003', 'admin_funding_url': ''}. PI: Peter J. Cavnar. Award: $126123.
Start: 2026-07-24T00:00:00.
PROJECT SUMMARY:
Neutrophils (polymorphonuclear leukocytes, PMNs) are the most abundant circulating leukocytes and serve as
the first responders to infection and injury. Upon activation by pro-inflammatory stimuli, including formyl-Met-
Leu-Phe (fMLF), IL-8, C5a, TNF-α, and LTB4, neutrophils perform essential functions such as adhesion,
chemotaxis, degranulation, and the generation of reactive oxygen species (respiratory burst) to eliminate
pathogens. However, excessive neutrophil activity contributes to chronic inflammation and tissue damage in
diseases such as rheumatoid arthritis, systemic lupus erythematosus, and Alzheimer’s disease. Understanding
the mechanisms that regulate neutrophil function is critical for developing targeted therapies for these conditions.
Dopamine (DA), a key neurotransmitter in the central nervous system, has recently emerged as an important
modulator of peripheral immune responses. While DA’s role in regulating adaptive immune cells has been well
documented, its influence on innate immune cells, particularly neutrophils, remains poorly understood.
Contributing to this lack of research is vital because neutrophils, through their potent inflammatory
responses, are critical to the pathology of infectious and chronic inflammatory diseases. Moreover, the
proposed research is significant because our results will have broader therapeutic implications, particularly
given the widespread use of dopaminergic drugs to treat conditions such as depression, addiction,
schizophrenia, bipolar disorder, and neurodegenerative diseases. The goal of this R16 SuRE proposal is to
elucidate dopaminergic regulation of neutrophil function using both primary human neutrophils and the HL-60
neutrophil-like cell model through the following aims:
AIM 1: Determine the regulation of dopamine receptor expression in primary human neutrophils and HL-60 cells
in response to inflammatory stimuli. We will quantify DA receptor mRNA and membrane expression using RT-
qPCR and flow cytometry after treatment with fMLF, C5a, IL-8, TNF-α, and LTB4.
AIM 2: Characterize DA and DA receptor subtype agonists on integrin activation, adhesion, chemotaxis,
degranulation, and respiratory burst in response to fMLF, C5a, IL-8, TNF-α, and LTB4 in both HL-60 cells and
primary human neutrophils.
This study will be the first to comprehensively characterize dopaminergic signaling in neutrophils under
inflammatory conditions. The findings will enhance our understanding of neuroimmune regulation and could
inform therapeutic strategies to mitigate inflammation in autoimmune and neurodegenerative diseases.document fetched 2026-08-02 08:24