Allergen cleavage by effector cell-derived proteases regulates allergic inflammation.
The key event of allergic inflammation, allergen-induced crosslinking of mast cell-bound IgE antibodies, is accompanied by release of inflammatory mediators, cytokines, and proteases, in particular beta-tryptase. We provide evidence that protease-mediated cleavage of allergens represents a mechanism that regulates allergen-induced mast cell activation. When used in molar ratios as they occur in vivo, purified beta-tryptase cleaved major grass and birch pollen allergens, resulting in defined peptide fragments as mapped by mass spectrometry. Tryptase-cleaved allergens showed reduced IgE reactivity and allergenic activity. The biological relevance is demonstrated by the fact that lysates from activated human mast cells containing tryptase levels as they occur in vivo cleaved allergens. Additionally, protamine, an inhibitor of heparin-dependent effector cell proteases, augmented allergen-induced release of mediators from effector cells. Protease-mediated allergen cleavage may represent an important mechanism for terminating allergen-induced effector cell activation.
Rauter
Ingrid
I
Division of Immunopathology, Department of Pathophysiology, Center for Physiology and Pathophysiology, Medical University of Vienna, Austria.
Krauth
Maria-Theresa
MT
Flicker
Sabine
S
Gieras
Anna
A
Westritschnig
Kerstin
K
Vrtala
Susanne
S
Balic
Nadja
N
Spitzauer
Susanne
S
Huss-Marp
Johannes
J
Brockow
Knut
K
Darsow
Ulf
U
Ring
Johannes
J
Behrendt
Heidrun
H
Semper
Hans
H
Valent
Peter
P
Valenta
Rudolf
R
D000485:Allergens / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D029662:Betula; D015550:Cell Degranulation; D045744:Cell Line, Tumor; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008407:Mast Cells / Q000378:metabolism; D008969:Molecular Sequence Data; D031784:Phleum; D010940:Plant Proteins / Q000737:chemistry / Q000378:metabolism; D011058:Pollen; D011479:Protamines / Q000378:metabolism; D051381:Rats; D012697:Serine Endopeptidases / Q000378:metabolism*; D053802:Tryptases
D000485:Allergens; D010940:Plant Proteins; D011479:Protamines; D012697:Serine Endopeptidases; C509223:Tpsab1 protein, rat; C509221:Tpsb2 protein, rat; D053802:Tryptases