δ Tryptase Is Expressed in Multiple Human Tissues, and a Recombinant Form Has Proteolytic Activity

Wang, Hong Wei; McNeil, H P; Husain, Ahsan; Liu, Ke; Tedla, Nicodemus; Thomas, Paul S.; Raftery, Mark J.; King, Garry C.; Cai, Zhao Yan; Hunt, John

doi:10.4049/jimmunol.169.9.5145

Cited by 39 publications

(36 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although numerous MCs contain hTryptase ␦ mRNA (26), this serine protease is less enzymatically active than mMCP-7 and hTryptase ␤1. It therefore remains to be determined whether hTryptase ␦ is functional in vivo.…”

Section: Mc-restricted Granule Proteases and Proteoglycansmentioning

confidence: 99%

Mast Cell-restricted Tryptases: Structure and Function in Inflammation and Pathogen Defense

McNeil

Adachi

Stevens

2007

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Mast cells (MCs) are highly specialized immune cells present in mammals and in lower organisms that predate the development of adaptive immunity. The strong evolutionary pressure to retain MCs for >500 million years suggests critical roles for these cells in our survival. In support of this conclusion, no human has been identified to date that lacks MCs, despite the adverse roles of MCs in systemic anaphylaxis and varied inflammatory disorders. MCs express numerous lineage-restricted neutral proteases, and four members of the chromosome 17A3.3 family of tryptases are preferentially expressed in mouse MCs. The anatomical location of MCs at host-environment interfaces has raised the possibility that some of these enzymes are evolutionally conserved because they are needed for combating infectious organisms. Here we review recent insights into the structure and function of MC tryptases in inflammation and host defense against bacteria and other infectious organisms. MC-restricted Granule Proteases and ProteoglycansA characteristic morphologic feature of mammalian mast cells (MCs) 3 is their electron-dense secretory granules, which contain serglycin proteoglycans (1, 2) bearing heparin (for review see Ref. 3) and chondroitin sulfates diB and E (4, 5). Heparin is the most negatively charged molecule in the body, and each rat and mouse peritoneal MC contains ϳ25 pg of this glycosaminoglycan, thereby explaining the avidity of MCs for cationic dyes (6). The repeating Ser-Gly sequence in serglycin where its glycosaminoglycans are attached cannot be cleaved by any known protease. This protease resistance feature is biologically relevant because the primary function of serglycin proteoglycans in MCs is to provide a scaffold for formation of macromolecular complexes with the cell's varied granule proteases. When properly folded, a positively charged face forms on the surface of each granule protease that allows it to bind tightly to the proteoglycan's negatively charged glycosaminoglycans (7-9).The proteases packaged in the secretory granules of mouse MCs include carboxypeptidase A3 (CPA3), granzyme B, cathepsin G, neuropsin, transmembrane tryptase/tryptase ␥/protease serine member S (Prss) 31, mouse MC protease (mMCP) 1-10, and mMCP-11/Prss34. Definitive evidence of the importance of heparin-containing serglycin proteoglycans in the packaging of specific cassettes of proteases in the MC's granules came with the characterization of N-deacetylase/Nsulfotransferase-2 (NDST-2)-null mice (10, 11). NDST-2 is essential for heparin biosynthesis and is preferentially expressed in MCs. Because of the loss of fully sulfated heparin, the MCs in the skin and peritoneal cavities of NDST-2-null mice store reduced amounts of mMCP-6 and almost no CPA3, mMCP-4, and mMCP-5, even though all four MC-restricted protease genes are transcribed at normal rates. The accumulated data led to the current view that serglycin proteoglycans are essential for the post-translational processing and granule accumulation of most, if not all, proteases stor...

show abstract

Section: Mc-restricted Granule Proteases and Proteoglycansmentioning

confidence: 99%

Mast Cell-restricted Tryptases: Structure and Function in Inflammation and Pathogen Defense

McNeil

Adachi

Stevens

2007

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…The gene locus of human tryptase in the chromosome 16p13.3 is far more complex than originally thought: there are two major forms, -and -tryptases, which can be divided further into 1-and 2-forms and 1-, 2-and 3-forms. Furthermore, additional forms include -, -and -tryptases [19,20,199,207,214] of which -tryptase is a functionally and structurally distinct membrane-bound enzyme in mast cells that can eYciently be inactivated by 1 -proteinase inhibitor [208,214], -tryptase is expressed in airway epithelial cells but apparently not markedly in mast cells [207], and -tryptase has marked amino acid similarity with -and -tryptases but is truncated by 40 amino acids in the carboxyterminal end and cannot hydrolyze the canonical tryptase substrate N-p-tosyl-Gly-Pro-Lys-p-nitronilide [199]. There is, however, a report showing that -tryptase gene is a pseudogene without transcription in human mast cells in vitro [119].…”

Section: Mast Cell Serine Proteinases In Psoriasismentioning

confidence: 99%

Is there a role for mast cells in psoriasis?

et al. 2008

View full text Add to dashboard Cite

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.

show abstract

“…The protein is highly expressed in intestine and various tumor cell lines. Human δ-tryptase, a product of the TPSD1 gene, is another variant which originally was named mMCP-7 like tryptase, but it has 40 amino acids deleted from the C-terminal relative to α/β-tryptases [31]. Whether the protein is highly expressed as an active protease is uncertain [32,31].…”

Section: Introductionmentioning

confidence: 99%

Active monomers of human β-tryptase have expanded substrate specificities

Fukuoka

Schwartz

2007

International Immunopharmacology

View full text Add to dashboard Cite

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.

show abstract

δ Tryptase Is Expressed in Multiple Human Tissues, and a Recombinant Form Has Proteolytic Activity

Cited by 39 publications

References 28 publications

Mast Cell-restricted Tryptases: Structure and Function in Inflammation and Pathogen Defense

Mast Cell-restricted Tryptases: Structure and Function in Inflammation and Pathogen Defense

Is there a role for mast cells in psoriasis?

Active monomers of human β-tryptase have expanded substrate specificities

Contact Info

Product

Resources

About