Exploring dopamine's influence on human neutrophil inflammatory responses

The National Institute of Allergy and Infectious Diseases awarded the University of West Florida $126,123 on July 24, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to conduct research exploring dopamine's influence on human neutrophil inflammatory responses.

The project investigates dopaminergic regulation of neutrophil function using both primary human neutrophils and the HL-60 neutrophil-like cell model. The research aims to determine dopamine receptor expression in these cells in response to inflammatory stimuli, with broader implications for understanding neutrophil pathology in infectious and chronic inflammatory diseases such as rheumatoid arthritis, systemic lupus erythematosus, and Alzheimer's disease. Results are expected to inform therapeutic development, particularly given widespread clinical use of dopaminergic drugs for depression, addiction, schizophrenia, bipolar disorder, and neurodegenerative diseases.

Performance takes place in Pensacola, Florida, with project completion scheduled for June 30, 2030. This is a project grant, a standard assistance type under the program. The University of West Florida serves as the prime recipient; the award carries no sub-recipient pass-through activity.

Abstract

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.