TY - JOUR
T1 - Mast cell-derived proteases control allergic inflammation through cleavage of IgE
AU - Rauter, Ingrid
AU - Krauth, Maria Theresa
AU - Westritschnig, Kerstin
AU - Horak, Friedrich
AU - Flicker, Sabine
AU - Gieras, Anna
AU - Repa, Andreas
AU - Balic, Nadja
AU - Spitzauer, Susanne
AU - Huss-Marp, Johannes
AU - Brockow, Knut
AU - Darsow, Ulf
AU - Behrendt, Heidrun
AU - Ring, Johannes
AU - Kricek, Franz
AU - Valent, Peter
AU - Valenta, Rudolf
N1 - Funding Information:
Supported by grants F1804, F1809, F1815, and T165-B09 of the Austrian Science Fund.
PY - 2008/1
Y1 - 2008/1
N2 - Background: Cross-linking of mast cell-bound IgE releases proinflammatory mediators, cytokines, and proteolytic enzymes and is a key event in allergic inflammation. Objective: We sought to study the effect of proteases released on effector cell activation on receptor-bound IgE and their possible role in the regulation of allergic inflammation. Methods: Using molar ratios of purified recombinant tryptase and human IgE, we studied whether tryptase can cleave IgE. Similar experiments were performed with mast cell lysates in the presence or absence of protease inhibitors. IgE cleavage products were detected in supernatants of allergen cross-linked, cultivated mast cells and in tissue fluids collected from patients' skin after IgE-mediated degranulation. The effects of protamine, an inhibitor of heparin-dependent proteases on IgE-mediated allergic in vivo skin inflammation in human subjects were studied. Results: We show that β-tryptase, a major protease released during mast cell activation, cleaves IgE. IgE degradation products were detected in tryptase-containing tissue fluids collected from sites of allergic inflammation. The biologic significance of this mechanism is demonstrated by in vivo experiments showing that protease inhibition enhances allergic skin inflammation. Conclusion: We suggest that IgE cleavage by effector cell proteases is a natural mechanism for controlling allergic inflammation.
AB - Background: Cross-linking of mast cell-bound IgE releases proinflammatory mediators, cytokines, and proteolytic enzymes and is a key event in allergic inflammation. Objective: We sought to study the effect of proteases released on effector cell activation on receptor-bound IgE and their possible role in the regulation of allergic inflammation. Methods: Using molar ratios of purified recombinant tryptase and human IgE, we studied whether tryptase can cleave IgE. Similar experiments were performed with mast cell lysates in the presence or absence of protease inhibitors. IgE cleavage products were detected in supernatants of allergen cross-linked, cultivated mast cells and in tissue fluids collected from patients' skin after IgE-mediated degranulation. The effects of protamine, an inhibitor of heparin-dependent proteases on IgE-mediated allergic in vivo skin inflammation in human subjects were studied. Results: We show that β-tryptase, a major protease released during mast cell activation, cleaves IgE. IgE degradation products were detected in tryptase-containing tissue fluids collected from sites of allergic inflammation. The biologic significance of this mechanism is demonstrated by in vivo experiments showing that protease inhibition enhances allergic skin inflammation. Conclusion: We suggest that IgE cleavage by effector cell proteases is a natural mechanism for controlling allergic inflammation.
KW - Allergy
KW - allergic inflammation
KW - mast cells/basophils
KW - proteases
UR - http://www.scopus.com/inward/record.url?scp=38149006143&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2007.08.015
DO - 10.1016/j.jaci.2007.08.015
M3 - Article
C2 - 17904627
AN - SCOPUS:38149006143
SN - 0091-6749
VL - 121
SP - 197
EP - 202
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 1
ER -