Journal Article Epublish 2 citations
PubMed: 39372553 DOI: 10.1007/s12195-024-00813-2
THP-1 Macrophages Limit Neutrophil Transendothelial Migration in a Model Infection.
Cell Mol Bioeng 17(4):279-293
Authors: Aitana Ignes-Romeu, Hannah K Weppner, Tanisha Kaur, Maya Singh, Laurel E Hind
Affiliations
- Department of Chemical and Biological Engineering, University of Colorado - Boulder, Boulder, CO 80303 USA.
- Present Address: Department of Bioengineering, University of Washington, Seattle, WA 98195 USA.
Abstract
Introduction
Dysregulated neutrophil function plays a significant role in the pathology of infections, cancer, cardiovascular diseases, and autoimmune disorders. Neutrophil activity is influenced by various cell populations, including macrophages, which are crucial regulators. However, the exact role of human macrophages in controlling neutrophil function remains unclear due to a scarcity of studies utilizing human cells in physiologically relevant models.
Methods
We adapted our "Infection-on-a-Chip" microfluidic device to incorporate macrophages within the collagen extracellular matrix, allowing for the study of interactions between human neutrophils and macrophages in a context that mimics in vivo conditions. The integration of THP-1 macrophages was optimized and their effect on the endothelial lumen was characterized, focusing on permeability and structural integrity. The device was then employed to examine the influence of macrophages on neutrophil response to infection with the bacterial pathogen Pseudomonas aeruginosa.
Results
Integration of THP-1 macrophages into the microfluidic device was successfully optimized, showing no increase in endothelial permeability or structural damage. The presence of macrophages was found to significantly reduce neutrophil transendothelial migration in response to Pseudomonas aeruginosa infection.
Conclusions
Our findings highlight the regulatory role of macrophages in modulating neutrophil responses, suggesting potential therapeutic targets to control neutrophil function in various diseases. The modified microfluidic platform offers a valuable tool for mechanistic studies into macrophage-neutrophil interactions in disease contexts.
Supplementary Information
The online version contains supplementary material available at 10.1007/s12195-024-00813-2.
MeSH
Cells, Macrophages, Microfluidics, Neutrophils, Infections