Mast Cells Promote Macrophage Polarization to M1-like Phenotype through a Tryptase-dependent Process

Mast cells (MCs) activate and support macrophage proliferation in inflammatory microenvironments. However, the role of MCs in regulating macrophage polarization under normal physiological conditions remains poorly understood. In this study, we used conditioned medium from the human MC line HMC-1 (HMC-1 CM) to examine its effect on macrophage polarization. HMC-1 CM was intro-duced at various stages: during the initiation of polarization into M1 and M2 phenotypes, after polarization, and to undifferentiated M0 macrophages. Additionally, we investigated the role of MC-derived tryptase in macrophage polarization using a tryptase inhibitor. Our findings show that HMC-1 CM significantly stimulated M1 marker expression in M0 macrophages when applied at the onset of culture. Moreover, HMC-1 CM increased the expression of Tgfb and Il10 in both M0 and M1-like macrophages, an effect that was diminished by the tryptase inhibitor. These results suggest that tryptase derived from MCs plays a crucial role in mediating macrophage polarization.