Mast cell tryptases

Dybendal X Guttormsen AB, Elsayed S, Askeland 48 B, Harboe T, Florvaag E Screening for mast cell tryptase and serum IgE antibodies in 18 patients with anaphylactic shock during general anaesthesia. 

Mastocytosis is recognized in most patients because of the presence of characteristic cutaneous lesions [10]. A positive Darier s sign and/or histological examination of the skin using metachromatic stains, or by immunohistochemistry using antibodies to mast cell tryptase, helps confirm the diagnosis of cutaneous disease. 

Ludolph-Hauser D, Rueff F, Fries C, et al Con- 40 stitutively raised serum concentrations of mast-cell tryptase and severe anaphylactic reactions to Hyme-noptera stings. Lancet 2001 357 361-362. 

Tryptase is at the present moment the main clinical marker for anaphylaxis and mastocytosis. There are two major human mast cells tryptases, a- and (3-tryptase, encoded by two genes located at chromosome 16. The haploid genotype for tryptase is (3a or (3(3.25% of individuals are a-tryptase-deficient a-tryptase shows a 90% amino acid sequence identity with (3-tryptase. 

Schwartz LB, Yunginger JW, Miller J, Bokhari R, Dull D Time course of appearance and disappearance of human mast cell tryptase in the circulation after anaphylaxis. J Clin Invest 1989 83 1551-1555. 

Brockow K. Vieluf D. Puschel K. Grosch J. Ring J Increased postmortem serum mast cell tryptase in a fatal anaphylactoid reaction to nonionic radiocontrast medium. J Allergy Clin Immunol 1999 104 237-238. Delage C, Irey HC Anaphylactic deaths a clinico-pathologic study of 43 cases. J Forensic Sci 1972 17 525. 

Cairns, J.A. and Walls, A.F. (1996) Mast cell tryptase is a mitogen for epithelial cells. Journal of Immunology 156, 275-283. 

Srinivasan et al. (2006) continuation of Srinivasan et al., 1996) Same study population 10 CD subjects who supplemented GFD with 50 g oats/day for 3 months Immune responses of in vitro duodenal mucosal culture treated with Abs against HLA D-related, Ki-67, CD25, CD54, ICAM-1, and mast cell tryptase None of the patients developed clinical or lab evidence of adverse effects Distribution of intestinal HLA-DR expression was not affected Number of CD25 and tryptase positive cells was not altered Distribution and intensity of ICAM-1 staining unchanged No evidence of immune activation from oats supplementation... 

A number of 1-substituted 2(l//)-pyrazinone derivatives show antithrombotic activity as selective inhibitors of the tissue Factor Vila complex <2003BML23I9> and were examined as mast cell tryptase inhibitors <2004BML48I9>. As a curious effect, dihydropyrazines proved to show DNA strand-breakage activity <2005CPB1359>. 

The sections are incubated for 1 hr with the primary monoclonal antibody, mouse antihuman mast cell tryptase antibody (DAKO), diluted 1 200 with 1% BSA/PBS. They are washed for 10 min in PBS using magnetic stirring, incubated with biotinylated antimouse antibody for 15 min, and washed in PBS. This is followed by adding avidin-biotin-horse-radish peroxidase for 15 min. A Vector DAB Substrate kit is applied to develop the reaction product by using nickel-DAB (5 min developing time) according to the manufacturer s instructions. This step yields a black reaction product at sites of mast cell tryptase. 

In addition to the use in the synthesis of potential hepatitis C drugs, microwave-assisted chemistry has also been used in the synthesis of mast cell tryptase inhibitors, thrombin inhibitors, and Factor Xa inhibitors. The trypsin-like serine protease tryptase is the major secretory product of human mast cells and has been implicated as an inflammatory mediator in a number of conditions, especially asthma. Once released upon mast cell activation, the tryptase cleaves substrates that otherwise cause smooth muscle relaxation and thereby bronchi- and vasodilation. It is therefore not surprising that numerous reports on low molecular weight tryptase inhibitors have appeared. 

Inhibitors Against Human Mast Cell Tryptase ... 

I 3.2 Inhibitors Against Human Mast Cell Tryptase A Potential Approach to Attack Asthma ... 

The in-vitro inhibition activity of the synthesized target compounds against human mast cell tryptase is summarized in Tables 3.2.1 and 3.2.2 Compound 8, which contains aminomethyl benzyl moieties as head groups, was the most potent of the pyran series (type I), with a Ki value of 1.3 nM. Compared with 8, the tryptase inhibitors with aminomethylcyclohexyl substituents (17, 18, and 21), were 100-fold (Ki = 130 nM), 60-fold (Ki = 75 nM), and approximately 90-fold (Ki = 120 nM) less... 

Inhibitors Against Human Mast Cell Tryptase A Potential Approach to Attack Asthma Tab. 3.2.1. The synthesized type II target inhibitors 9, and 24-29, and their K values. 

Neutral and acidic serine proteases released from mast cells-tryptase MCX may damage type IV collagen and the intercellular matrix. Eosinophil chemotactic factors... 

During inflammation, degranulation of immune cells releases serine proteases that pass through and bind to the capillary wall. Increased levels of Bik suppress these immune cell proteases and protect the extracellular matrix in arterial walls and connective tissue [4]. Bik inhibits phagocytic destruction of cells. Bik has been shown to inhibit elastases, granzymes A and K [4, 57], Mast cell tryptases (J3- and a-tetrameric forms with a molecular weight of 134 kDa) are resistant to aprotinin [58]. Lymphocytes serine esterase TL2 is not inhibited by Bik [59]. 

Inflammation leads to vasodilation that damages the endothelial and epithelial layers, thus promoting vascular disease [4], Kallikrein, neutrophil elastase, and mast cell tryptase release kinins from kininogens. Kinins are... 

Payne V, Kam PCA. Mast cell tryptase A review of its physiology and clinical significance. 

Tsuji, A., Akamatsu, T., Nagamune, H., Matsuda, Y. (1994). Identification of targeting proteinase for rat alpha 1-macro-globulin in vivo. Mast-cell tryptase is a major component of the alpha 1-macroglobulin-proteinase complex endoc dosed into rat liver lysosomes. Biochem. J. 298 79-85. 

An 81-year-old man underwent CT scanning of the head with intravenous contrast enhancement (100 ml of the non-ionic contrast medium iopamidol). After the injection he complained of sweating and nausea and had a cardiorespiratory arrest. Immediate resuscitation and intravenous dexamethasone and adrenaline were not successful. Mast cell tryptase activity in a sample taken 4 hours after death was high. At autopsy, the coronary and pulmonary arteries were patent. The right heart chambers were moderately enlarged. The lungs were hyperemic and edematous and there was obstructive edema of the larynx. 

Fisher MM, Baldo BA. The diagnosis of fatal anaphylactic reactions during anaesthesia employment of immunoassays for mast cell tryptase and drug-reactive IgE antibodies. Anaesth Intensive Care 1993 21(3) 353-7. 

Heparin has been used in enzyme purification such as recombinant human mast cell tryptase. The purified enzyme is fully active [12]. Heparin-based affinity chromatography also permitted the isolation of growth factors such as basic fibroblast growth factor (bFGF). The affinity is lower when bFGF is complexed with acidic gelatin [13]. The elution of synthetic TFPI (tissue factor pathway inhibitor) peptidic fragments on immobilized heparin has allowed one to find the peptidic sequence responsible for the TFPI-heparin interaction [14]. 

A. L. Niles, M. Maffit, M. Haak-Frendscho, C. J. Whee-less, et al., Recombinant mast cell tryptase Stable expression in Pichia pastoris and purification of fully active enzyme, Biotechnol. Appl. Biochem. 28 125 (1998). 

Alter, S.C., Kramps, J.A., Janoff, A. and Schwartz, L.B. (1990). Interactions of human mast cell tryptase with biological protease inhibitors. Arch. Biochem. Biophys. 276, 26-31. 

Caughcy, G.H., Leidig, F., Viro, N.F. andNadel, J.A. (1988). Substance P and vasoactive intestinal peptide degradation by mast cell tryptase and chymase. J. Pharmacol. Exp. Ther. 244, 133-137. 

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