Tryptase Precursors Are Preferentially and Spontaneously Released, Whereas Mature Tryptase Is Retained by HMC-1 Cells, Mono-Mac-6 Cells, and Human Skin-Derived Mast Cells

Schwartz, Lawrence B.; Min, Hae‐Ki; Ren, Shuling; Xia, Han‐Zhang; Hu, Jiang; Zhao, Wei; Moxley, George; Fukuoka, Yoshihiro

doi:10.4049/jimmunol.170.11.5667

Cited by 105 publications

(103 citation statements)

References 41 publications

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“…6 Thus baseline immunoreactive tryptase in serum is now thought to consist mainly of pro-α and pro-β tryptases, with the latter making the major contribution, given that levels of immunoreactive tryptase change little in individuals without α genes. 6 The situation can be expected to be similar in anaphylaxis. Because α tryptase is not stored, it will not contribute to an increase in tryptase levels with acute mast cell degranulation.…”

Section: A Wide Functional Divide Between α and β Tryptasesmentioning

confidence: 99%

Tryptase genetics and anaphylaxis

Caughey¹

2006

Journal of Allergy and Clinical Immunology

137

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Tryptases secreted by tissue mast cells and basophils can enter the bloodstream. In human subjects tryptases are encoded by several genes and alleles, including α, β, γ, and δ. Common variations include complete absence of α genes. Until recently, α tryptase was considered to be the major tryptase secreted at baseline and in mastocytosis. However, lack of α tryptase genes has little effect on circulating tryptase levels, which are now thought mainly to consist of inactive pro-β tryptase secreted constitutively rather than stored in granules with mature tryptases. Pro-β tryptase levels thus might reflect total body mast cell content. In contrast, mature β tryptase can increase transiently in severe systemic anaphylaxis and confirm the diagnosis. However, it might fail to increase in food anaphylaxis or might increase nonspecifically in samples acquired after death. Thus pro-and mature β tryptase measurements are useful but associated with false-negative and false-positive results, which need to be considered in drawing clinical conclusions in cases of suspected anaphylaxis.

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Section: A Wide Functional Divide Between α and β Tryptasesmentioning

confidence: 99%

Tryptase genetics and anaphylaxis

Caughey¹

2006

Journal of Allergy and Clinical Immunology

137

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“…There is, however, a report showing that -tryptase gene is a pseudogene without transcription in human mast cells in vitro [119]. Nevertheless, inactive -and -protryptases are constitutively secreted and active -tryptase is the principal enzyme that is packed and stored in large quantities in the secretory granules of mast cells [64,169]. Human -tryptase is a ring-like tetramer with four active centers facing towards the central oval pore [144].…”

Section: Mast Cell Serine Proteinases In Psoriasismentioning

confidence: 99%

Is there a role for mast cells in psoriasis?

et al. 2008

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Mast cells have traditionally been considered as eVector cells in allergy but during the last decade it has been realized that mast cells are essentially involved in the mechanisms of innate and acquired immunity. Upon activation by anaphylactic, piecemeal degranulation or degranulation-independent mechanisms mast cells can secrete rapidly or slowly a number of soluble mediators, such as serine proteinases, histamine, lipid-derived mediators, cytokines, chemokines and growth factors. Mast cells can express cell surface co-stimulatory receptors and ligands, and they can express MHC class II molecules and thereby present antigens. These soluble factors and cell surface molecules can interact with other cells, such as endothelial cells, keratinocytes, sensory nerves, neutrophils, T cell subsets and antigen presenting cells which are essential eVectors in the development of skin inXammation. Besides promoting inXammation, mast cells may attempt in some circumstances to suppress the inXammation and epidermal growth but the regulation between suppressive and proinXammatory mechanisms is unclear. Psoriasis is characterized by epidermal hyperplasia and chronic inXammation where tryptase-and chymase-positive MC TC mast cells are activated early in the developing lesion and later the cells increase in number in the upper dermis with concomitant expression of cytokines and TNF superfamily ligands as well as increased contacts with neuropeptide-containing sensory nerves. Due to the intimate involvement of mast cells in immunity and chronic inXammation the role of mast cells in psoriasis is discussed in this review.

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“…Asp 215 dominantly restricts the substrate specificity of engineered mature α-tryptase. Although mature β-tryptase is stored in secretory granules of mast cells, unprocessed α-protryptases are inactive and spontaneously secreted from mast cells [27]. Of potential interest to the human system is that disrupting the mouse N-deacetylase/N-sulfotransferase-2 gene, which is necessary to express fully sulfated heparin [28], showed reductions in the amounts of tryptase, chymase(s) and carboxypeptidase A3 in mast cells.…”

Section: Introductionmentioning

confidence: 99%

Active monomers of human β-tryptase have expanded substrate specificities

Fukuoka

Schwartz

2007

International Immunopharmacology

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Abstractβ-Tryptase, a product of the TPSAB1 and TPSB2 genes, is a trypsin-like serine protease that is a major and selective component of the secretory granules of all human mast cells, accounting for as much as 25% of cell protein. Once mast cells are activated, β-tryptase is released along with histamine and heparin proteoglycan. β-Tryptase is a unique enzyme with a homotetrameric structure in which active sites face into the central cavity of the four monomers, stabilized by heparin-proteoglycan. This structure makes β-tryptase resistant to most biological inhibitors of serine proteases. Without stabilization, at neutral pH β-tryptase converts to inactive monomers. Tryptase levels are elevated in bronchoalveolar lavage (BAL) fluid obtained from atopic asthmatics and in serum during systemic anaphylactic shock. Several synthetic small molecular weight β-tryptase inhibitors reduced Aginduced airway hypersensitivity in animals, suggesting β-tryptase is involved in the pathogenesis of airway inflammation. Although the major biologic substrate(s) of β-tryptase remain ambiguous, the protease can digest several proteins of potential biologic importance, including fibrinogen, fibronectin, pro-urokinase, pro-matrix metalloprotease-3 (proMMP-3), protease activated receptor-2 (PAR2) and complement component C3. Recently, monomers of β-tryptase with enzymatic activity have been detected in vitro. Here we discuss how β-tryptase monomers with enzymatic activity were identified as well as their potential role in vivo.

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Tryptase Precursors Are Preferentially and Spontaneously Released, Whereas Mature Tryptase Is Retained by HMC-1 Cells, Mono-Mac-6 Cells, and Human Skin-Derived Mast Cells

Cited by 105 publications

References 41 publications

Tryptase genetics and anaphylaxis

Tryptase genetics and anaphylaxis

Is there a role for mast cells in psoriasis?

Active monomers of human β-tryptase have expanded substrate specificities

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