THP-1 Macrophages Limit Neutrophil Transendothelial Migration in a Model Infection.

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.