{"doi":"10.4049/jimmunol.1201736","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","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>","journal":"The Journal of Immunology","year":2012,"id":31277,"datarank":5.735382220973024,"base_score":5.0106352940962555,"endowment":5.0106352940962555,"self_citation_contribution":0.7515952941144385,"citation_network_contribution":4.983786926858586,"self_endowment_contribution":0.7515952941144385,"citer_contribution":4.983786926858586,"corpus_percentile":null,"corpus_rank":null,"citation_count":149,"citer_count":117,"citers_with_citation_signal":106,"citers_with_endowment":106,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":167982,"name":"Lisbeth Jensen","orcid":null,"position":1,"is_corresponding":false},{"id":124785,"name":"Annette G Hansen","orcid":null,"position":2,"is_corresponding":false},{"id":167984,"name":"Duygu Duman","orcid":null,"position":3,"is_corresponding":false},{"id":167985,"name":"Mustafa Tekin","orcid":null,"position":4,"is_corresponding":false},{"id":123750,"name":"Jens C Jensenius","orcid":null,"position":5,"is_corresponding":false},{"id":123751,"name":"Steffen Thiel","orcid":null,"position":6,"is_corresponding":false},{"id":123749,"name":"Søren E Degn","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":5.0106352940962555,"endowment":5.0106352940962555,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"22966085","pmcid":null,"openalex_id":"https://openalex.org/W2109529646","authors":[],"funders":[],"total_grants":0,"fwci":8.7244,"citation_percentile":0.98506864,"influential_citations":13,"citation_trend":[{"year":2013,"count":30},{"year":2014,"count":16},{"year":2015,"count":22},{"year":2016,"count":17},{"year":2017,"count":14},{"year":2018,"count":11},{"year":2019,"count":9},{"year":2020,"count":4},{"year":2021,"count":6},{"year":2022,"count":10},{"year":2023,"count":4},{"year":2024,"count":3},{"year":2025,"count":2},{"year":2026,"count":1}],"oa_status":"closed","license":"https://academic.oup.com/pages/standard-publication-reuse-rights","oa_locations":[{"url":"https://academic.oup.com/jimmunol/article-pdf/189/8/3957/61743924/1201736.pdf","host_type":"publisher"},{"url":"https://doi.org/10.4049/jimmunol.1201736","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/22966085","host_type":"repository"},{"url":"https://pure.au.dk/portal/en/publications/c285a8dc-0d53-4a2d-a15e-0e89b0905255","host_type":""}],"fields_of_study":["Complement system in diseases","Trypanosoma species research and implications","Platelet Disorders and Treatments","Medicine","Biology","Abdominal Muscles","Abnormalities, Multiple","Animals","Blepharoptosis","Codon, Nonsense","Complement Pathway, Alternative","Complement Pathway, Mannose-Binding Lectin","Craniofacial Abnormalities","Craniosynostoses","Cryptorchidism","Developmental Disabilities","Eye Abnormalities","Heart Defects, Congenital","Hip Dislocation, Congenital","Humans","Mannose-Binding Protein-Associated Serine Proteases","Strabismus","Transcriptional Activation","Carnevale syndrome","Malpuech facial clefting syndrome","Oculopalatoskeletal syndrome"],"mesh_terms":["Abdominal Muscles","Abnormalities, Multiple","Animals","Blepharoptosis","Developmental Disabilities","Complement Pathway, Alternative","Craniosynostoses","Cryptorchidism","Eye Abnormalities","Heart Defects, Congenital","Hip Dislocation, Congenital","Humans","Strabismus","Transcriptional Activation","Codon, Nonsense","Craniofacial Abnormalities","Complement Pathway, Mannose-Binding Lectin","Mannose-Binding Protein-Associated Serine Proteases"],"keywords":["Lectin pathway","Mannan-binding lectin","Ficolin","Complement system","MASP1","Complement component 2","Alternative complement pathway","C3-convertase","C-type lectin","Biology","Factor H","Proteases","Complement factor B","Lectin","Chemistry","Serine protease","Biochemistry","Genetics","Protease","Enzyme","Immune system"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-09T06:47:19.862435Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}