Immunopathology
Constantin A. Bona, Francisco A. Bonilla in Textbook of Immunology, 2019
A variety of degradative enzymes may generate new mediators from local substrates (complement, kininogen, coagulation factors, etc.). These propagate and/or modify an ongoing inflammatory process. The neutral proteases tryptase and chymase distinguish two major types of mast cells (see above). Tryptase is a serine protease with Mr 31–35 kDa, it is active as a tetramer and has activity similar to trypsin. The physiologic role of tryptase is unclear. It cleaves vasoactive intestinal peptide (VIP) and a few other neuropeptides with bronchodilator activity, hence tryptase may lead indirectly to bronchoconstriction. Tryptase may also be mitogenic for fibroblasts. Chymase is actually a group of enzymes related to cathepsin G, elastase, and cytotoxic T cell granzymes (see Chapter 6). These enzymes have Mr 28–32 kDa and have activity similar to α-chymotrypsin. Chymase converts angiotensin I to angiotensin II, it degrades bradykinin, it cleaves neuropeptides VIP and substance P (and others), and may increase mucus secretion in airways. Mast cell carboxypeptidase has Mr 36 kDa and activity similar to carboxypeptidase A. It has been shown to degrade neurotensin, enkephalins, and other neuropeptides. Like other neutral proteases, its role in allergic inflammation requires clarification.
Mast Cell Mediators and their Effect on Airway Smooth Muscle
Devendra K. Agrawal, Robert G. Townley in Inflammatory Cells and Mediators in Bronchial Asthma, 2020
Human mast cells contain two major neutral proteases, tryptase and chymase, which represent the major protein component of these cells. These proteases may be specific markers for mast cells and mast cell activation. Indeed, tryptase levels are elevated in blood of patients with both nonacute systemic mastocytosis and ongoing anaphylaxis, in skin chamber fluid after allergen challenge, in nasal lavage fluid after nasal allergen challenge, and in bronchoalveolar lavage fluid after airway allergen challenge.50–53 Moreover, baseline bronchoalveolar lavage fluid tryptase levels have also been reported to be higher in allergic asthmatics vs. normal controls.53
Immune Control of Myometrial Contractility: Role of Mast Cells
Robert E. Garfield, Thomas N. Tabb in Control of Uterine Contractility, 2019
There are two types of mast cells in the rat and murine system, mucosal mast cells (MMC) and connective tissue type mast cells (CTMC). In humans, the mast cells are identified by specific serine protease content of tryptase and chymase. The subclass MCT (tryptase) and MCTC (tryptase-chymase) designate the two subpopulations of human mast cells.3–7
Positive correlation between blood pressure or heart rate and chymase-dependent angiotensin II-forming activity in circulating mononuclear leukocytes measured by new ELISA
Published in Clinical and Experimental Hypertension, 2018
Keisuke Okamura, Tetsu Okuda, Kazuyuki Shirai, Hidenori Urata
Human chymase is a serine proteinase that forms angiotensin II, and it has been isolated from the hearts obtained by the heart transplantation program of The Cleveland Clinic Foundation (1,2). Human cardiovascular organs have a much higher content of chymase compared with angiotensin-converting enzyme (3), suggesting that it makes an important contribution to local formation of angiotensin II, but not to circulating angiotensin II. On the other hand, ACE is more important for generation of circulating angiotensin II because chymase is inactivated by potent serine proteinase inhibitors in the blood. However, the physiological and/or pathological roles of chymase in humans remain unclear due to the lack of a clinically available chymase inhibitor. Animal studies have indicated that local angiotensin II formation makes a significant contribution to atherosclerosis in hamsters on a high-fat diet (4) since treatment with a chymase inhibitor (SUN-C8257) significantly reduced aortic atherosclerotic plaque (4). Also, another chymase inhibitor (TEI-E548) significantly decreased mortality in hamsters with myocardial infarction (5).
Role of chymase in blood pressure control, plasma and tissue angiotensin II, renal Haemodynamics, and excretion in spontaneously hypertensive rats
Published in Clinical and Experimental Hypertension, 2021
Malwina M. Roszkowska-Chojecka, Iwona Baranowska, Olga Gawrys, Janusz Sadowski, Agnieszka Walkowska, Malgorzata Kalisz, Anna Litwiniuk, Elzbieta Kompanowska-Jezierska
Our observations first provide the evidence for the common belief that the activity of chymostatin-sensitive enzymes can raise ANG II content in the plasma. It was proposed that the mechanism can be the release of chymase-generated ANG II from tissue compartments containing RAS into systemic circulation. The observation that, in patients, antihypertensive effectiveness of ACE inhibitors is often limited may depend on the fact that these agents do not block chymase-mediated ANG II formation (37–39). Overall, chymase blockade could be conceived as a promising approach in the treatment of hypertensive patients, especially those resistant to therapy with ACE-inhibitors. Moreover, blockade of chymase alone could be tried in patients in whom treatment with ACE-inhibitors is contraindicated.
Serum concentration of renin-angiotensin system components in association with ACE I/D polymorphism among hypertensive subjects in response to ACE inhibitor therapy
Published in Clinical and Experimental Hypertension, 2019
Mariyana Hristova, Spaska Stanilova, Lyuba Miteva
The serum quantity of alternative AngII producing enzyme - chymase was also higher in patients with uncontrolled EH than in patients with good therapeutic control of BP using ACEi (responders). In our previous preliminary study, an elevation of serum chymase in EH patients was observed, although the significant differences between cases with uncontrolled and controlled EH had been not detected (25). In a larger group, enrolled for the current study, the higher circulation chymase levels among cases with uncontrolled EH than cases with controlled EH were also detected. In addition, 90% of investigated patients with uncontrolled EH showed higher chymase levels (above 27.4 pg/ml). These results suggest that higher chymase levels are significantly associated with more than 10-fold higher risk for an unfavorable effect of therapeutic blood pressure control with ACE inhibitor. Chymase, in contrast to ACE2, is expressed mainly by mast cells and is stored in the granules as an active enzyme. Receptor-mediated activation of mast cells resulted in degranulation and release of the contents into the microenvironment. The role of resident cardiac and perivascular mast cells, as well as chymase derived AngII in cardiovascular disease has been well documented previously (7,26,27). A recent clinical investigation showed the positive correlation between circulating mononuclear leukocytes chymase activity and various hypertension related parameters among patients who were not on antihypertensive drugs (28). Taken all together, we could suggest that a higher serum level of chymase is a reflection of higher local levels of the enzyme, released by activated mast cells.
Related Knowledge Centers
- Basophil
- Parasitism
- Serine Protease
- Hypertension
- Atherosclerosis
- Mast Cell
- Angiotensin
- Antigen
- Trichuris Muris