TY - JOUR
T1 - Protease-activated receptor-2 signaling triggers dendritic cell development
AU - Fields, Ryan C.
AU - Schoenecker, Jonathan G.
AU - Hart, Justin P.
AU - Hoffman, Maureane R.
AU - Pizzo, Salvatore V.
AU - Lawson, Jeffrey H.
N1 - Funding Information:
Supported by the American Heart Association, the National Cancer Institute, and the National Heart, Lung, and Blood Institute. J.L. is the recipient of a Clinician Scientist Award from the American Heart Association and Genentch.
PY - 2003/6/1
Y1 - 2003/6/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0038582714&partnerID=8YFLogxK
U2 - 10.1016/S0002-9440(10)64316-7
DO - 10.1016/S0002-9440(10)64316-7
M3 - Article
C2 - 12759239
AN - SCOPUS:0038582714
SN - 0002-9440
VL - 162
SP - 1817
EP - 1822
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 6
ER -