{"doi":"10.1084/jem.20090633","title":"Essential role of Mannose-binding lectin-associated serine protease-1 in activation of the complement factor D","abstract":"<jats:p>The complement system is an essential component of innate immunity, participating in the pathogenesis of inflammatory diseases and in host defense. In the lectin complement pathway, mannose-binding lectin (MBL) and ficolins act as recognition molecules, and MBL-associated serine protease (MASP) is a key enzyme; MASP-2 is responsible for the lectin pathway activation. The function of other serine proteases (MASP-1 and MASP-3) is still obscure. In this study, we generated a MASP-1– and MASP-3–deficient mouse model (Masp1/3−/−) and found that no activation of the alternative pathway was observed in Masp1/3−/− serum. Mass spectrometric analysis revealed that circulating complement factor D (Df) in Masp1/3−/− mice is a zymogen (pro-Df) with the activation peptide QPRGR at its N terminus. These results suggested that Masp1/3−/− mice failed to convert pro-Df to its active form, whereas it was generally accepted that the activation peptide of pro-Df is removed during its secretion and factor D constitutively exists in an active form in the circulation. Furthermore, recombinant MASP-1 converted pro-Df to the active form in vitro, although the activation mechanism of pro-Df by MASP-1 is still unclear. Thus, it is clear that MASP-1 is an essential protease of both the lectin and alternative complement pathways.</jats:p>","journal":"Journal of Experimental Medicine","year":2010,"id":33050,"datarank":0.8603826636969725,"base_score":5.087596335232384,"endowment":5.087596335232384,"self_citation_contribution":0.7631394502848576,"citation_network_contribution":0.09724321341211478,"self_endowment_contribution":0.7631394502848576,"citer_contribution":0.09724321341211478,"corpus_percentile":null,"corpus_rank":null,"citation_count":161,"citer_count":4,"citers_with_citation_signal":4,"citers_with_endowment":4,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":123118,"name":"Yumi Ishida","orcid":null,"position":1,"is_corresponding":false},{"id":123116,"name":"Daisuke Iwaki","orcid":null,"position":2,"is_corresponding":false},{"id":123117,"name":"Kazuko Kanno","orcid":null,"position":3,"is_corresponding":false},{"id":173768,"name":"Toshiyuki Suzuki","orcid":null,"position":4,"is_corresponding":false},{"id":123106,"name":"Yuichi Endo","orcid":null,"position":5,"is_corresponding":false},{"id":173769,"name":"Yoshimi Homma","orcid":null,"position":6,"is_corresponding":false},{"id":122928,"name":"Teizo Fujita","orcid":null,"position":7,"is_corresponding":false},{"id":123115,"name":"Minoru Takahashi","orcid":"0000-0001-7625-2448","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"20038603","pmcid":"PMC2812541","openalex_id":"https://openalex.org/W20038603","authors":[],"funders":[],"total_grants":0,"fwci":0.5642,"citation_percentile":0.77954291,"influential_citations":12,"citation_trend":[{"year":2013,"count":1}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://rupress.org/jem/article-pdf/207/1/29/1201278/jem_20090633.pdf","host_type":"BRONZE"},{"url":"https://rupress.org/jem/article-pdf/207/1/29/1201278/jem_20090633.pdf","host_type":"publisher"},{"url":"https://rupress.org/jem/article-pdf/207/1/29/1903180/jem_20090633.pdf","host_type":"publisher"},{"url":"http://sro.sussex.ac.uk/id/eprint/22972/","host_type":"journal"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2812541","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC2812541","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC2812541?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Organizational Change and Leadership","Education Systems and Policy","Leadership and Management in Organizations","Medicine","Biology","3T3-L1 Cells","Animals","Complement Factor D","Complement Pathway, Alternative","Complement Pathway, Mannose-Binding Lectin","Humans","Immunity, Innate","Lectins","Mannose-Binding Lectin","Mannose-Binding Protein-Associated Serine Proteases","Mice","Mice, Knockout","Ficolins"],"mesh_terms":["3T3-L1 Cells","Animals","Mice, Knockout","Humans","Mice","Complement Factor D","Lectins","Mannose-Binding Lectin","Complement Pathway, Alternative","Complement Pathway, Mannose-Binding Lectin","Mannose-Binding Protein-Associated Serine Proteases","Immunity, Innate","Ficolins"],"keywords":["Sustainability","Political science"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Responsible consumption and production"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-09T15:27:48.910433Z","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,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}