Protease-activated receptor-2 signaling triggers dendritic cell development.

Fields RC, Schoenecker JG, Hart JP, Hoffman MR, Pizzo SV, Lawson JH
Am J Pathol. 2003 162 (6): 1817-22

PMID: 12759239 · PMCID: PMC1868121 · DOI:10.1016/S0002-9440(10)64316-7

Dendritic cells (DC) are potent antigen-presenting cells that govern the effector cell responses of the immune system. DC are thought to continuously develop from circulating progenitors in a process that is accelerated by inflammatory stimuli. However, the physiological signals that regulate the development of DC from precursor cells have not been well defined. Here we show that a serine protease acting via protease-activated receptor-2 (PAR-2) stimulates the development of DC from bone marrow progenitor cells cultured in granulocyte-macrophage colony-stimulating factor and IL-4. DC fail to develop in bone marrow cultures treated with soy bean trypsin inhibitor, a serine protease inhibitor, but this inhibition is overcome by a PAR-2 agonist peptide. DC do not spontaneously develop from the bone marrow of PAR-2-deficient mice, but can be stimulated to do so by inflammatory mediators. These results suggest that endogenous serine proteases stimulate DC development in vitro. Thus, serine proteases may help trigger adaptive immune responses in vivo.

MeSH Terms (23)

Animals Bone Marrow Cells CD11c Antigen Cell Division Cells, Cultured Dendritic Cells Female Flow Cytometry Genotype Granulocyte-Macrophage Colony-Stimulating Factor Histocompatibility Antigens Class II Interleukin-4 Male Mice Mice, Inbred C57BL Mice, Knockout Oligopeptides Receptor, PAR-2 Receptors, Thrombin Signal Transduction Spleen Trypsin Inhibitor, Kunitz Soybean Tumor Necrosis Factor-alpha

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