Abstract
Mast cells are primary effector cells of allergy, and recruitment of mast cells in involved tissue is one of the key events in allergic inflammation. Tryptase is the most abundant secretory product of mast cells, but little is known of its influence on mast cell accumulation. Using mouse peritoneal model, cell migration assay, and flow cytometry analysis, we investigated role of tryptase in recruiting mast cells. The results showed that tryptase induced up to 6.7-fold increase in mast cell numbers in mouse peritoneum following injection. Inhibitors of tryptase, an antagonist of PAR-2 FSLLRY-NH2, and pretreatment of mice with anti-ICAM-1, anti-CD11a, and anti-CD18 antibodies dramatically diminished tryptase induced mast cell accumulation. On the other hand, PAR-2 agonist peptides SLIGRL-NH2 and tc-LIGRLO-NH2 provoked mast cell accumulation following injection. These implicate that tryptase induced mast cell accumulation is dependent on its enzymatic activity, activation of PAR-2, and interaction between ICAM-1 and LFA-1. Moreover, induction of trans-endothelium migration of mast cells in vitro indicates that tryptase acts as a chemoattractant. In conclusion, provocation of mast cell accumulation by mast cell tryptase suggests a novel self-amplification mechanism of mast cell accumulation. Mast cell stabilizers as well as PAR-2 antagonist agents may be useful for treatment of allergic reactions.
Highlights
Mast cell tryptase belongs to serine proteases and is almost exclusively located to the secretory granules of mast cells
Agonist peptides of protease activated receptor-2 (PAR-2), SLIGRL-NH2, and trans-cinnamoyl LIGRLONH2 as well as their reverse forms LRGILS-NH2 and tcOLRGIL-NH2 and Protease activated receptor (PAR)-2 antagonist peptide FSLLRY-NH2 were synthesized by CL Bio-Scientific Inc. (Xi An, China) with a purity >98% assessed by HPLC analysis
It was reported that histamine was able to induce chemotaxis of mast cells through histamine H4 receptor [14], suggesting a self-amplification mechanism of mast cell accumulation
Summary
Mast cell tryptase belongs to serine proteases and is almost exclusively located to the secretory granules of mast cells. It has been found that tryptase is capable of provoking microvascular leakage in the skin of guinea pigs [5], stimulating the release of histamine from dispersed human tonsil mast cells [6], and inducing recruitment of inflammatory cells to endothelium [7] and eosinophils and neutrophil in peritoneum of mice [8]. These observations implicate that this mast cell protease is likely to play a role in the pathogenesis of mast cell associated inflammation
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