Histamine as a mediator of cross-talk between human lung mast cells and macrophages

Histamine, a multifaceted inflammatory mediator released from mast cells and basophils, has long been recognized for its critical role in orchestrating various aspects of allergic responses. Historically, the role of macrophages in allergic disorders has been underestimated compared to other immune cells, such as mast cells, eosinophils, and basophils. These cells are the predominant immune cells in the human lung, both in healthy individuals and patients with asthma. Macrophages and mast cells are in proximity in human lung, suggesting a complex interplay between these cells in airway inflammation. In this study, we have investigated the effects of histamine on various functional aspects of highly purified macrophages from human lung (HLMs). Histamine caused a concentration-dependent release of pro-inflammatory cytokines (IL-6, TNF-α, IL-1β) from HLMs, through interaction with H1 receptor (HRH1) and induced the expression of IL-6 mRNA, but not of TNF-α and IL-1β mRNAs. Histamine rapidly caused the production of reactive oxygen species (ROS) and impaired autophagic process in HLMs. Moreover, histamine induced chemotaxis and altered the kinetic properties of HLMs. Finally, HRH1 gene expression was upregulated by histamine. Histamine activates several pro-inflammatory pathways of HLMs relevant in airway inflammation. Given the close proximity of macrophages and mast cells in human lung, these results suggest an interplay between these cells in which histamine, released by mast cells, may serve as a signalling molecule influencing several macrophage responses.