Triggering of protease-activated receptors (PARs) induces alternative M2 macrophage polarization with impaired plasticity

Publication date: October 2019Source: Molecular Immunology, Volume 114Author(s): Gerardo García-González, Alejandro Sánchez-González, Romel Hernández-Bello, Gloria M. González, Moisés Armides Franco-Molina, Erika Evangelina Coronado-Cerda, José Prisco Palma-NicolásAbstractProtease-activated receptors (PARs) have been described in a wide diversity of vertebrate cells, including human immune cells. Macrophages are pivotal cells in the host-pathogen interaction and their polarization in M1 or M2 cells has been described as a new central paradigm in the immune response to pathogens. In this context, we explored the involvement of PAR activation by serine proteases on M1/M2 macrophage differentiation and their impact on the Th1/Th2 cytokine profile in response to Mycobacterium tuberculosis antigen. Our results demonstrate that the serine proteases, thrombin and trypsin, induce interleukin (IL)-4 release from human monocytes, together with upregulation of the macrophage mannose receptor (CD206) in the same way that alternative M2a differentiated cells with M-CSF/IL-4. Protease stimulation of monocytes in the presence of PAR-1 (SCH-79797) or PAR-2 (FSLLRY-NH2) antagonists abolished IL-4 release from monocytes, whereas the use of the peptide agonist for PAR-1 (SFLLRNPNDKYEPF-NH2) or PAR-2 (SLIGKV-NH2) induced the secretion of IL-4 at a level comparable to thrombin or trypsin. When these protease-induced M2 macrophages from healthy human PPD + donors were co-cultured with...
Source: Molecular Immunology - Category: Allergy & Immunology Source Type: research