{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:50:07Z","timestamp":1791298207457,"version":"4.1.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2009,5,1]],"date-time":"2009-05-01T00:00:00Z","timestamp":1241136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>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 \u03b12-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 \u03b12-macroglobulin-bound chymase remains accessible to small substrates, including angiotensin I, with activity in serum that is stable with prolonged incubation. We used \u03b12-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 \u223c1 pM (30 pg\/ml), and reveals native chymase activity in serum of most subjects with systemic mastocytosis. \u03b12-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 \u03b12-macroglobulin is active, that the complex is an angiotensin-converting enzyme inhibitor-resistant reservoir of angiotensin II-generating activity, and that \u03b12-macroglobulin capture may be exploited in assessing systemic release of secreted peptidases.<\/jats:p>","DOI":"10.4049\/jimmunol.0900127","type":"journal-article","created":{"date-parts":[[2009,4,21]],"date-time":"2009-04-21T01:07:38Z","timestamp":1240276058000},"page":"5770-5777","source":"Crossref","is-referenced-by-count":44,"title":["\u03b12-Macroglobulin Capture Allows Detection of Mast Cell Chymase in Serum and Creates a Reservoir of Angiotensin II-Generating Activity"],"prefix":"10.1093","volume":"182","author":[{"given":"Wilfred W","family":"Raymond","sequence":"first","affiliation":[{"name":"Cardiovascular Research Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Stanford University School of Medicine , Stanford, CA 94305; the"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Makarova","sequence":"additional","affiliation":[{"name":"Veterans Health Research Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd M","family":"Wilson","sequence":"additional","affiliation":[{"name":"The Laboratory of Allergic Diseases of the National Institute of Allergy and Infectious Diseases , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melody C","family":"Carter","sequence":"additional","affiliation":[{"name":"The Laboratory of Allergic Diseases of the National Institute of Allergy and Infectious Diseases , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean D","family":"Metcalfe","sequence":"additional","affiliation":[{"name":"The Laboratory of Allergic Diseases of the National Institute of Allergy and Infectious Diseases , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George H","family":"Caughey","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute"},{"name":"Department of Medicine, University of California at San Francisco , San Francisco, CA 94143"},{"name":"Veterans Health Research Institute"},{"name":"Veterans Affairs Medical Center , San Francisco, CA 94121"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,5,1]]},"reference":[{"key":"2026012807043325600_R1","first-page":"8619","article-title":"Rapid conversion of angiotensin I to angiotensin II by neutrophil and mast cell proteinases.","volume-title":"J. 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