{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:48:04Z","timestamp":1791276484715,"version":"4.1.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2012,10,1]],"date-time":"2012-10-01T00:00:00Z","timestamp":1349049600000},"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":[[2012,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The lectin pathway of complement is an important component of innate immunity. Its activation has been thought to occur via recognition of pathogens by mannan-binding lectin (MBL) or ficolins in complex with MBL-associated serine protease (MASP)-2, followed by MASP-2 autoactivation and cleavage of C4 and C2 generating the C3 convertase. MASP-1 and MASP-3 are related proteases found in similar complexes. MASP-1 has been shown to aid MASP-2 convertase generation by auxiliary C2 cleavage. In mice, MASP-1 and MASP-3 have been reported to be central also to alternative pathway function through activation of profactor D and factor B. In this study, we present functional studies based on a patient harboring a nonsense mutation in the common part of the MASP1 gene and hence deficient in both MASP-1 and MASP-3. Surprisingly, we find that the alternative pathway in this patient functions normally, and is unaffected by reconstitution with MASP-1 and MASP-3. Conversely, we find that the patient has a nonfunctional lectin pathway, which can be restored by MASP-1, implying that this component is crucial for complement activation. We show that, although MASP-2 is able to autoactivate under artificial conditions, MASP-1 dramatically increases lectin pathway activity at physiological conditions through direct activation of MASP-2. We further demonstrate that MASP-1 and MASP-2 can associate in the same MBL complex, and that such cocomplexes are found in serum, providing a scenario for transactivation of MASP-2. Hence, in functional terms, it appears that MASP-1 and MASP-2 act in a manner analogous to that of C1r and C1s of the classical pathway.<\/jats:p>","DOI":"10.4049\/jimmunol.1201736","type":"journal-article","created":{"date-parts":[[2012,9,11]],"date-time":"2012-09-11T03:26:13Z","timestamp":1347333973000},"page":"3957-3969","source":"Crossref","is-referenced-by-count":143,"title":["Mannan-Binding Lectin-Associated Serine Protease (MASP)-1 Is Crucial for Lectin Pathway Activation in Human Serum, whereas neither MASP-1 nor MASP-3 Is Required for Alternative Pathway Function"],"prefix":"10.1093","volume":"189","author":[{"given":"S\u00f8ren E","family":"Degn","sequence":"first","affiliation":[{"name":"Department of Biomedicine, Aarhus University , DK-8000 Aarhus C,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisbeth","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University , DK-8000 Aarhus C,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette G","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University , DK-8000 Aarhus C,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duygu","family":"Duman","sequence":"additional","affiliation":[{"name":"Division of Pediatric Genetics, Ankara University School of Medicine , 06100 Ankara,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa","family":"Tekin","sequence":"additional","affiliation":[{"name":"Division of Pediatric Genetics, Ankara University School of Medicine , 06100 Ankara,","place":["Turkey"]},{"name":"John P. Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami , Miami, FL 33136"},{"name":"Dr. John T. Macdonald Department of Human Genetics, Miller School of Medicine, University of Miami , Miami, FL 33136"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens C","family":"Jensenius","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University , DK-8000 Aarhus C,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Thiel","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University , DK-8000 Aarhus C,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,10,15]]},"reference":[{"key":"2025032409290810500_r1","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/ni.1923","article-title":"Complement: a key system for immune surveillance and homeostasis","volume":"11","author":"Ricklin","year":"2010","journal-title":"Nat. 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