ArticleJournal of immunology (Baltimore, Md. : 1950)2009
Alpha 2-macroglobulin capture allows detection of mast cell chymase in serum and creates a reservoir of angiotensin II-generating activity.
Article in Journal of immunology (Baltimore, Md. : 1950), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 49 citations in OpenAlex.
- Metalloproteinases (MMPs) in hypertensive disorders: role, function, pharmacology, and potential strategies to mitigate pathophysiological changes.Frontiers in pharmacology · 2025Review
- Recombinant chymase inhibits fibrinolysis induced by endogenous plasmin in clotted human blood.Frontiers in immunology · 2025Article
- Engineering New Protease Inhibitors Using αMethods in molecular biology (Clifton, N.J.) · 2024Article
- Secretory and Membrane-Associated Biomarkers of Mast Cell Activation and Proliferation.International journal of molecular sciences · 2023Review
- Chymase Inhibition Resolves and Prevents Deep Vein Thrombosis Without Increasing Bleeding Time in the Mouse Model.Journal of the American Heart Association · 2023Article
- New Biomarkers in Anaphylaxis (Beyond Tryptase).Current treatment options in allergy · 2022Review
- Cathepsin G Activity as a New Marker for Detecting Airway Inflammation by Microscopy and Flow Cytometry.ACS central science · 2019Article
- IgE-Mediated Systemic Anaphylaxis And Its Association With Gene Polymorphisms Of ACE, Angiotensinogen And Chymase.Journal of asthma and allergy · 2019Article
- Multifunctional Role of Chymase in Acute and Chronic Tissue Injury and Remodeling.Circulation research · 2018Review
- Human Mesenchymal Stem Cell-Derived Microvesicles Prevent the Rupture of Intracranial Aneurysm in Part by Suppression of Mast Cell Activation via a PGE2-Dependent Mechanism.Stem cells (Dayton, Ohio) · 2016Article
- Mast cell proteases as pharmacological targets.European journal of pharmacology · 2016Review
- Biomarkers of the involvement of mast cells, basophils and eosinophils in asthma and allergic diseases.The World Allergy Organization journal · 2016Review
- Regulation of hepatocyte growth factor in mice with pneumonia by peptidases and trans-alveolar flux.PloS one · 2015Article
- Angiotensin-(1-12): a chymase-mediated cellular angiotensin II substrate.Current hypertension reports · 2014Review
- Mutational tail loss is an evolutionary mechanism for liberating marapsins and other type I serine proteases from transmembrane anchors.The Journal of biological chemistry · 2013Article
- Chymase inhibition as a pharmacological target: a role in inflammatory and functional gastrointestinal disorders?British journal of pharmacology · 2012Review
- Impact of Mast Cell Chymase on Renal Disease Progression.Current hypertension reviews · 2012Article
- The αvβ6 integrin modulates airway hyperresponsiveness in mice by regulating intraepithelial mast cells.The Journal of clinical investigation · 2012Article
- Mast cell proteases as protective and inflammatory mediators.Advances in experimental medicine and biology · 2011Review
- How immune peptidases change specificity: cathepsin G gained tryptic function but lost efficiency during primate evolution.Journal of immunology (Baltimore, Md. : 1950) · 2010Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
Abstract
Human chymase is a highly efficient angiotensin II-generating serine peptidase expressed by mast cells. When secreted from degranulating cells, it can interact with a variety of circulating antipeptidases, but is mostly captured by alpha(2)-macroglobulin, which sequesters peptidases in a cage-like structure that precludes interactions with large protein substrates and inhibitors, like serpins. The present work shows that alpha(2)-macroglobulin-bound chymase remains accessible to small substrates, including angiotensin I, with activity in serum that is stable with prolonged incubation. We used alpha(2)-macroglobulin capture to develop a sensitive, microtiter plate-based assay for serum chymase, assisted by a novel substrate synthesized based on results of combinatorial screening of peptide substrates. The substrate has low background hydrolysis in serum and is chymase-selective, with minimal cleavage by the chymotryptic peptidases cathepsin G and chymotrypsin. The assay detects activity in chymase-spiked serum with a threshold of approximately 1 pM (30 pg/ml), and reveals native chymase activity in serum of most subjects with systemic mastocytosis. alpha(2)-Macroglobulin-bound chymase generates angiotensin II in chymase-spiked serum, and it appears in native serum as chymostatin-inhibited activity, which can exceed activity of captopril-sensitive angiotensin-converting enzyme. These findings suggest that chymase bound to alpha(2)-macroglobulin is active, that the complex is an angiotensin-converting enzyme inhibitor-resistant reservoir of angiotensin II-generating activity, and that alpha(2)-macroglobulin capture may be exploited in assessing systemic release of secreted peptidases.
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Registered trials
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