Protease-activated receptor-2 signaling triggers dendritic cell development.
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.
Fields
Ryan C
RC
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Schoenecker
Jonathan G
JG
Hart
Justin P
JP
Hoffman
Maureane R
MR
Pizzo
Salvatore V
SV
Lawson
Jeffrey H
JH
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D039521:CD11c Antigen / Q000096:biosynthesis; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005838:Genotype; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D015847:Interleukin-4 / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009842:Oligopeptides / Q000494:pharmacology; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D014360:Trypsin Inhibitor, Kunitz Soybean / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D039521:CD11c Antigen; D000949:Histocompatibility Antigens Class II; D009842:Oligopeptides; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; D014409:Tumor Necrosis Factor-alpha; C099570:seryl-leucyl-isoleucyl-glycyl-arginyl-leucine; D015847:Interleukin-4; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D014360:Trypsin Inhibitor, Kunitz Soybean