Angiotensin I Conversion by Human and Rat Chymotryptic Proteinases

Wintroub, Bruce U.; Schechter, Norman B.; Lazarus, Gerald S.; Kaempfer, C E; Schwartz, Lawrence B.

doi:10.1111/1523-1747.ep12264144

Cited by 145 publications

(69 citation statements)

References 22 publications

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“…Human skin chymotrypsin-like proteinase cleavage of the cutaneous epidermal-dermal junction at the lamina lucida (26) is an example of a direct action of a mast cell enzyme, while mast cell kinin-generating activity (27) and tryptase cleavage of the third component of complement (28) and fibrinogen (29) illustrate indirect actions of mast cell enzymes. If the human mast cell chymase is indeed identical to the human skin chymotrypsinlike proteinase, the Km and K., for AI conversion would be 6.6 X 10-5 M and 50 s-', respectively (8). These kinetics are consistent with a reaction of potential biologic significance.…”

Section: Resultsmentioning

confidence: 57%

“…Recently, a 30-35,000-mol-wt chymotrypsin-like activity has been isolated from high ionic strength extracts of human skin (7) and found in 15-fold higher levels in skin of patients with mastocytosis (7). Like other enzymes with chymotryptic specificity, the human skin chymotryptic proteinase hydrolyzes the phe8-hisg bond of the decapeptide angiotensin I (Al)' to form angiotensin II (AII) (8,9). It is of interest that the human skin enzyme carries out this reaction as efficiently as angiotensin-converting enzyme (ACE) (8).…”

Section: Introductionmentioning

confidence: 99%

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A human lung mast cell chymotrypsin-like enzyme. Identification and partial characterization.

Wintroub¹,

Kaempfer²,

Schechter³

et al. 1986

J. Clin. Invest.

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We have used a high performance liquid chromatography assay, which detects chymotryptic cleavage of the phe8-his, bond of angiotensin I to yield angiotensin II, in order to examine human lung mast cells for the presence of chymotryptic activity. Mast cells, purified from human lung by enzymatic dispersion, countercurrent elutriation, and Percoll gradient centrifugation, were lysed or challenged with goat anti-human IgE. In multiple experiments angiotensin II-converting activity was detected in lysates of 10-99% pure mast cell preparations. Regression analysis of net percent release values of histamine and the angiotensin I-converting activity from dose-response experiments demonstrated a correlation between the two parameters, indicating that the chymotrypsin-like enzyme is a constituent of the mast cell secretory granule. The chymotryptic activity was completely inhibited by i0' M phenylmethylsulfonylfluoride but not by 1O-3 M Captopril, and the pH optimum of activity was 7.5-9.5. Gel filtration of released material separated the activity from tryptase and demonstrated an approximate molecular weight of 30-35,000. The mast cell enzyme, like a human skin chymotrypsinlike proteinase, can be distinguished from leukocyte cathepsin G by lack of susceptibility to inhibition by bovine pancreatic trypsin inhibitor. Thus, an enzyme with limited chymotryptic specificity is present in human lung mast cells. The Michaelis constant of the enzyme for angiotensin I of 6.0 X 10-5 M is similar to that of endothelial cell angiotensin-converting enzyme and is consistent with a reaction of physiologic importance.

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Section: Resultsmentioning

confidence: 57%

Section: Introductionmentioning

confidence: 99%

A human lung mast cell chymotrypsin-like enzyme. Identification and partial characterization.

Wintroub¹,

Kaempfer²,

Schechter³

et al. 1986

J. Clin. Invest.

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“…Heparin facilitates the processing of prochymase [10,11] and β-protryptase [12] by dipeptidylpeptidase I (DPPI, Cathepsin C), a cysteine protease. Chymase converts angiotensin I to angiotensin II [13,14], processes type I procollagen to collagen fibrils [15] and degrades various cytokines [16]. Cathepsin G is serine protease expressed by MC TC cells [17] as well as by neutrophils and monocytes.…”

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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“…However, the changes in chymase expression levels and activity in the tissues during burn wound healing remain unclear. Human chymase differs to the chymase in the majority of other animals with regard to substrate specificity, with the exceptions of monkeys, dogs and hamsters (16)(17)(18) …”

Section: Introductionmentioning

confidence: 99%

Expression and activity levels of chymase in mast cells of burn wound tissues increase during the healing process in a hamster model

Dong

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. The present study aimed to investigate the changes in the expression levels and activity of mast cell chymase in the process of burn wound healing in a hamster model of deep second-degree burn. The hamster model was established by exposing a ~3 cm diameter area of bare skin to hot water (75˚C) for 0, 6, 8, 10 or 12 sec. Tissue specimens were collected 24 h after burning and histological analysis revealed that hot water contact for 12 sec was required to produce a deep second-degree burn. Quantitative polymerase chain reaction and a radioimmunoassay were used to the determine changes in chymase mRNA expression levels and activity. The mRNA expression levels and activity of chymase were increased in the burn wound tissues when compared with the normal skin. However, no statistically significant differences were observed in mast cell chymase activity amongst the various post-burn stages. Chymase mRNA expression levels peaked at day 1 post-burn, subsequently decreasing at days 3 and 7 post-burn and finally increasing again at day 14 post-burn. In summary, a hamster model of deep second-degree burn can be created by bringing the skin into contact with water at 75˚C for 12 sec. Furthermore, the mRNA expression levels and activity of chymase in the burn wound tissues increased when compared with those in normal skin tissues. IntroductionSkin wound healing is a complex multifactorial process, involving inflammation, cell proliferation, cell migration, re-epithelialization, angiogenesis, extracellular matrix deposition and remodeling (1,2). Burn wounds have a long healing period, and are the most representative persistent wounds for use in the study of skin wound healing. Deep second-degree burn wounds exhibit spontaneous epithelial regeneration through the proliferation and migration of the skin appendages under the wound and the epidermal cells around the wound margin (3). The healing period is relatively long; thus, deep second-degree burns are useful for the experimental study of burn wounds. Animal models of burn wounds have been used to study various pathological changes and healing mechanisms involved in the burn wound healing process (4).Burn-induced tissue ischemia and inflammation can increase the number of mast cells in burn tissues (5) and stimulate mast cells to release vasoactive substances by degranulation (6). Mast cells play a role in the acute inflammatory phase and participate in wound healing together with fibroblasts (7,8). Once activated, mast cells degranulate and release histamine, heparin and a variety of enzymes, such as chymase, cathepsin G and hydroxy peptidase A (9). Chymase is closely associated with tissue fibrosis.Chymase is an α-chymase-like serine protease that is involved in numerous physiological and pathophysiological processes. One of the most important functions of chymase is the regulation of angiotensin (Ang)II generation. In addition, chymase promotes myocardial and skin fibroblast proliferation (10,11), the release of transforming growth factor-β1 bound to the extracel...

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Angiotensin I Conversion by Human and Rat Chymotryptic Proteinases

Cited by 145 publications

References 22 publications

A human lung mast cell chymotrypsin-like enzyme. Identification and partial characterization.

A human lung mast cell chymotrypsin-like enzyme. Identification and partial characterization.

Active monomers of human β-tryptase have expanded substrate specificities

Expression and activity levels of chymase in mast cells of burn wound tissues increase during the healing process in a hamster model

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