{"doi":"10.4049/jimmunol.165.2.1030","title":"Complement-Dependent Acute-Phase Expression of C-Reactive Protein and Serum Amyloid P-Component","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>The acute-phase response (APR) is regulated by TNF-α, IL-1β, and IL-6 acting alone, in combination, or in concert with hormones. The anaphylotoxin C5a, generated during complement activation, induces in vitro the synthesis of these cytokines by leukocytes and of acute-phase proteins by HepG2 cells. However, there is no clear evidence for a role of C5a or any other complement activation product in regulation of the APR in vivo. In this study, using human C-reactive protein (CRP) transgenic mice deficient in C3 or C5, we investigated whether complement activation contributes to induction of the acute-phase proteins CRP and serum amyloid P-component (SAP). Absence of C3 or C5 resulted in decreased LPS-induced up-regulation of the CRP transgene and the mouse SAP gene. Also, LPS induced both the IL-1β and IL-6 genes in normocomplementemic mice, but in complement-deficient mice it significantly induced only IL-6. Like LPS injection, activation of complement by cobra venom factor led to significant elevation of serum CRP and SAP in normocomplementemic mice but not in complement-deficient mice. Injection of recombinant human C5a into human CRP transgenic mice induced the IL-1β gene and caused significant elevation of both serum CRP and SAP. However, in human CRP transgenic IL-6-deficient mice, recombinant human C5a did not induce the CRP nor the SAP gene. Based on these data, we conclude that during the APR, C5a generated as a consequence of complement activation acts in concert with IL-6 and/or IL-1β to promote up-regulation of the CRP and SAP genes.</jats:p>","journal":"The Journal of Immunology","year":2000,"id":37277,"datarank":4.394452900566458,"base_score":4.454347296253507,"endowment":4.454347296253507,"self_citation_contribution":0.6681520944380261,"citation_network_contribution":3.726300806128432,"self_endowment_contribution":0.6681520944380261,"citer_contribution":3.726300806128432,"corpus_percentile":null,"corpus_rank":null,"citation_count":85,"citer_count":77,"citers_with_citation_signal":69,"citers_with_endowment":69,"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,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":187150,"name":"Frederik W van Ginkel","orcid":null,"position":1,"is_corresponding":false},{"id":19081,"name":"Yue Wang","orcid":"0000-0002-0278-2347","position":2,"is_corresponding":false},{"id":187151,"name":"Jerry R McGhee","orcid":null,"position":3,"is_corresponding":false},{"id":187152,"name":"John E Volanakis","orcid":null,"position":4,"is_corresponding":false},{"id":187149,"name":"Alexander J Szalai","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":4.454347296253507,"endowment":4.454347296253507,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"10878380","pmcid":null,"openalex_id":"https://openalex.org/W2095812219","authors":[],"funders":[{"funder_name":"NIAID NIH HHS","grant_id":"AI 42183","title":null}],"total_grants":1,"fwci":2.5166,"citation_percentile":0.89518957,"influential_citations":0,"citation_trend":[{"year":2012,"count":2},{"year":2013,"count":3},{"year":2014,"count":4},{"year":2015,"count":3},{"year":2016,"count":2},{"year":2017,"count":4},{"year":2018,"count":5},{"year":2019,"count":5},{"year":2020,"count":1},{"year":2021,"count":1},{"year":2022,"count":1},{"year":2023,"count":3},{"year":2024,"count":1}],"oa_status":"bronze","license":"https://academic.oup.com/pages/standard-publication-reuse-rights","oa_locations":[{"url":"https://journals.aai.org/jimmunol/article-pdf/165/2/1030/1118853/1030.pdf","host_type":"journal"},{"url":"https://journals.aai.org/jimmunol/article-pdf/165/2/1030/1118853/1030.pdf","host_type":"BRONZE"},{"url":"https://journals.aai.org/jimmunol/article-pdf/165/2/1030/1118853/1030.pdf","host_type":"publisher"},{"url":"https://academic.oup.com/jimmunol/article-pdf/165/2/1030/62129657/1030.pdf","host_type":"publisher"},{"url":"https://doi.org/10.4049/jimmunol.165.2.1030","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/10878380","host_type":"repository"}],"fields_of_study":["Complement system in diseases","Erythrocyte Function and Pathophysiology","Blood properties and coagulation","Biology","Medicine","Acute-Phase Reaction","Animals","C-Reactive Protein","Complement Activation","Complement C5a","Complement Inactivator Proteins","Complement System Proteins","Dose-Response Relationship, Immunologic","Elapid Venoms","Gene Expression Regulation","Humans","Injections, Intraperitoneal","Interleukin-1","Interleukin-6","Lipopolysaccharides","Male","Mice","Mice, Inbred C57BL","Mice, Inbred DBA","Mice, Knockout","Mice, Transgenic","Serum Amyloid P-Component","Transgenes","Up-Regulation"],"mesh_terms":["Acute-Phase Reaction","Serum Amyloid P-Component","Animals","C-Reactive Protein","Complement System Proteins","Complement Activation","Complement Inactivator Proteins","Dose-Response Relationship, Immunologic","Elapid Venoms","Gene Expression Regulation","Humans","Injections, Intraperitoneal","Interleukin-1","Lipopolysaccharides","Male","Mice, Inbred C57BL","Mice, Inbred DBA","Mice, Transgenic","Interleukin-6","Up-Regulation","Complement C5a","Mice, Knockout","Transgenes","Mice"],"keywords":["Serum amyloid P component","Complement system","Acute-phase protein","Transgene","Genetically modified mouse","Complement component 3","Complement factor B","Serum amyloid A","Complement factor I","Biology","In vivo","Alternative complement pathway","Recombinant DNA","Immunology","Molecular biology","Inflammation","C-reactive protein","Gene","Antibody","Biochemistry"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-10T19:00:12.421822Z","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":[]}