{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:59:33Z","timestamp":1753891173032,"version":"3.41.2"},"reference-count":86,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T00:00:00Z","timestamp":1731456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Complement activation split products are signatures of many immunopathological disorders. Among the laboratory findings observed in these diseases, a reduction in the level of circulating intact complement components can be mentioned, and this change has also been detected in envenomation by multiple Africanized honeybee (Apis mellifera) stings. Although envenomation by these animals elicits diverse life-threatening reactions, the capacity of bee venom (AmV) to activate the human complement system remains elusive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and findings<\/jats:title><jats:p>By coupling immunochemical and functional approaches, it was observed that AmV strongly consumes components of the alternative pathway (AP) of the complement system in normal human serum (NHS). Additionally, AmV interfered with classical (CP) and lectin pathways (LP) activities. In parallel, a high increase in Ba fragment levels was detected, suggesting that the changes in AP activity were due to its activation. Furthermore, an increase in the level of the C1s-C1INH complex and a decrease in the physiological level of MASP1-C1INH suggested that CP and LP were also activated in the presence of AmV. Strikingly, NHS exposed to increasing AmV concentrations varying from 5 to 1000 \u00b5g\/mL presented a high generation of C3a, C4a and C5a anaphylatoxins, and sC5b-9 complexes assembly, thus reinforcing that AmV triggers complement activation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results show that AmV is a strong complement activator. This activation presents a mixed profile, with a predominance of AP activation. This suggests that complement split products can play important roles in the envenomation by Africanized honeybee, as they could induce diverse immunopathological events observed in patients and may also dictate patient clinical prognosis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2024.1463471","type":"journal-article","created":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T11:34:09Z","timestamp":1731497649000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Africanized honeybee venom (Apis mellifera) promotes human complement activation split products storm"],"prefix":"10.3389","volume":"15","author":[{"given":"Felipe","family":"Silva de Fran\u00e7a","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo","family":"de Oliveira Orsi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dayanne Carla","family":"Fernandes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thyago Bispo","family":"Leonel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denise V.","family":"Tambourgi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,11,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01308","article-title":"Complement nomenclature-deconvoluted","volume":"10","author":"Bohlson","year":"2019","journal-title":"Front Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0168-x","article-title":"New insights into the immune functions of complement","volume":"19","author":"Reis","year":"2019","journal-title":"Nat Rev Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.3MIR0220-270R","article-title":"Complement: Bridging the innate and adaptive immune systems in sterile inflammation","volume":"108","author":"Lo","year":"2020","journal-title":"J Leukoc Biol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/0161-5890(89)90057-6","article-title":"Non-enzymic activation of the fifth component of human complement, by oxygen radicals. Some properties of the activation product, C5b-like C5","volume":"26","author":"Vogt","year":"1989","journal-title":"Mol Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/nm1419","article-title":"Generation of C5a in the absence of C3: a new complement activation pathway","volume":"12","author":"Huber-Lang","year":"2006","journal-title":"Nat Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/s0003-4975(03)00878-6","article-title":"ONO-6818, a novel, potent neutrophil elastase inhibitor, reduces inflammatory mediators during simulated extracorporeal circulation","volume":"76","author":"Yoshimura","year":"2003","journal-title":"Ann Thorac Surg"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903678","article-title":"Molecular intercommunication between the complement and coagulation systems","volume":"185","author":"Amara","year":"2010","journal-title":"J Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.9.6307","article-title":"Generation of anaphylatoxins by human beta-tryptase from C3, C4, and C5","volume":"180","author":"Fukuoka","year":"2008","journal-title":"J Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1103029","article-title":"Factor VII-activating protease is activated in multiple trauma patients and generates anaphylatoxin C5a","volume":"188","author":"Kanse","year":"2012","journal-title":"J Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.10.018","article-title":"Intracellular complement activation sustains T cell homeostasis and mediates effector differentiation","volume":"39","author":"Liszewski","year":"2013","journal-title":"Immunity"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abf2489","article-title":"Mitochondrial C5aR1 activity in macrophages controls IL-1\u03b2 production underlying sterile inflammation","volume":"6","author":"Niyonzima","year":"2021","journal-title":"Sci Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1502287","article-title":"Intracellular activation of complement 3 is responsible for intestinal tissue damage during mesenteric ischemia","volume":"198","author":"Satyam","year":"2017","journal-title":"J Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.652242","article-title":"C5a-C5aR1 axis activation drives envenomation immunopathology by the snake Naja annulifera","volume":"12","author":"Silva de Fran\u00e7a","year":"2021","journal-title":"Front Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0804207","article-title":"Targeted disruption of the gene encoding the murine small subunit of carboxypeptidase N (CPN1) causes susceptibility to C5a anaphylatoxin-mediated shock","volume":"182","author":"Mueller-Ortiz","year":"2009","journal-title":"J Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.578069","article-title":"Therapeutic lessons to be learned from the role of complement regulators as double-edged sword in health and disease","volume":"11","author":"de Boer","year":"2020","journal-title":"Front Immunol"},{"key":"B16","article-title":"Essential role of the C5a receptor in E coli-induced oxidative burst and phagocytosis revealed by a novel lepirudin-based human whole blood model of inflammation","volume":"100","author":"Mollnes","year":"2002","journal-title":"Blood"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.8.5543","article-title":"Hematin promotes complement alternative pathway-mediated deposition of C3 activation fragments on human erythrocytes: potential implications for the pathogenesis of anemia in malaria","volume":"179","author":"Pawluczkowycz","year":"2007","journal-title":"J Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2013.05.221","article-title":"An international serum standard for application in assays to detect human complement activation products","volume":"56","author":"Bergseth","year":"2013","journal-title":"Mol Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2020.112876","article-title":"Avoiding ambient air in test tubes during incubations of human whole-blood minimizes complement background activation","volume":"487","author":"Storm","year":"2020","journal-title":"J Immunol Methods"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.2100308","article-title":"Air bubbles activate complement and trigger hemostasis and C3-dependent cytokine release ex vivo in human whole blood","volume":"207","author":"Storm","year":"2021","journal-title":"J Immunol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1093\/cei\/uxad091","article-title":"Increased thromboinflammatory load in hereditary angioedema","volume":"214","author":"Gramstad","year":"2023","journal-title":"Clin Exp Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-05-502229","article-title":"C3a modulates IL-1\u03b2 secretion in human monocytes by regulating ATP efflux and subsequent NLRP3 inflammasome activation","volume":"122","author":"Asgari","year":"2013","journal-title":"Blood"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad1210","article-title":"T helper 1 immunity requires complement-driven NLRP3 inflammasome activity in CD4+ T cells","volume":"352","author":"Arbore","year":"2016","journal-title":"Science"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1706818114","article-title":"Inhibition of complement C5 protects against organ failure and reduces mortality in a baboon model of Escherichia coli sepsis","volume":"114","author":"Keshari","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B25","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1038\/s41467-017-00414-w","article-title":"Exploiting a novel conformational switch to control innate immunity mediated by complement protein C3a","volume":"8","author":"Lohman","year":"2017","journal-title":"Nat Commun"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4400826","article-title":"Complement binding is an early feature of necrotic and a rather late event during apoptotic cell death","volume":"8","author":"Gaipl","year":"2001","journal-title":"Cell Death Differ"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200425045","article-title":"Complement activation by necrotic cells in normal plasma environment compares to that by late apoptotic cells and involves predominantly IgM","volume":"34","author":"Ciurana","year":"2004","journal-title":"Eur J Immunol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.02.023","article-title":"Endocytosis and recycling of immune complexes by follicular dendritic cells enhances B cell antigen binding and activation","volume":"38","author":"Heesters","year":"2013","journal-title":"Immunity"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.10.5833","article-title":"Cutting edge: C3d functions as a molecular adjuvant in the absence of CD21\/35 expression","volume":"172","author":"Haas","year":"2004","journal-title":"J Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1172\/JCI15409","article-title":"Increased C5a receptor expression in sepsis","volume":"110","author":"Riedemann","year":"2002","journal-title":"J Clin Invest"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1111\/imm.13585","article-title":"Alternative pathway dysregulation in tissues drives sustained complement activation and predicts outcome across the disease course in COVID-19","volume":"168","author":"Siggins","year":"2023","journal-title":"Immunology"},{"key":"B32","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1186\/s12974-018-1217-2","article-title":"Complement components are upregulated and correlate with disease progression in the TDP-43Q331K mouse model of amyotrophic lateral sclerosis","volume":"15","author":"Lee","year":"2018","journal-title":"J Neuroinflammation"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2022.102979","article-title":"The complement system and human autoimmune diseases","volume":"137","author":"Coss","year":"2023","journal-title":"J Autoimmun"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1160\/TH11-08-0554","article-title":"Complement activation in patients with isolated antiphospholipid antibodies or primary antiphospholipid syndrome","volume":"107","author":"Breen","year":"2012","journal-title":"Thromb Haemost"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0047095","article-title":"Complement depletion deteriorates clinical outcomes of severe abdominal sepsis: a conspirator of infection and coagulopathy in crime","volume":"7","author":"Ren","year":"2012","journal-title":"PloS One"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2018.08.013","article-title":"Complement component consumption in sepsis correlates better with hemostatic system parameters than with inflammatory biomarkers","volume":"170","author":"Lendak","year":"2018","journal-title":"Thromb Res"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1136\/tsaco-2018-000217","article-title":"Early complementopathy predicts the outcomes of patients with trauma","volume":"4","author":"Li","year":"2019","journal-title":"Trauma Surg Acute Care Open"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2007.09.034","article-title":"Genetic analysis of complement C1s deficiency associated with systemic lupus erythematosus highlights alternative splicing of normal C1s gene","volume":"45","author":"Amano","year":"2008","journal-title":"Mol Immunol"},{"key":"B39","article-title":"Severe and fatal mass attacks by 'killer' bees (Africanized honey bees\u2013Apis mellifera scutellata) in Brazil: clinicopathological studies with measurement of serum venom concentrations","volume":"87","author":"Fran\u00e7a","year":"1994","journal-title":"Q J Med"},{"key":"B40","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1080\/10937404.2023.2300786","article-title":"Standardized guidelines for Africanized honeybee venom production needed for development of new apilic antivenom","volume":"27","author":"Oliveira Orsi","year":"2024","journal-title":"J Toxicol Environ Health B Crit Rev"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1678-9199-19-18","article-title":"Lesions caused by Africanized honeybee stings in three cattle in Brazil","volume":"19","author":"Caldas","year":"2013","journal-title":"J Venomous Anim Toxins Including Trop Dis"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1292\/jvms.15-0183","article-title":"An accidental fatal attack on domestic pigeons by honeybees in Bangladesh","volume":"77","author":"Rahman","year":"2015","journal-title":"J Vet Med Sci"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.toxicon.2017.06.007","article-title":"Massive attack of honeybee on macaws (Ara ararauna and Ara chloropterus) in Brazil - A case report","volume":"136","author":"Milbradt","year":"2017","journal-title":"Toxicon"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1638\/2020-0037","article-title":"Clinical observations of bee envenomation in toucans","volume":"52","author":"Dislich","year":"2021","journal-title":"J Zoo Wildl Med"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2024.107666","article-title":"Fatal Africanized bee attack in captive non-human primates (Saimiri ustus and Sapajus libidinosus)","volume":"241","author":"Mac\u00eado","year":"2024","journal-title":"Toxicon"},{"key":"B46","unstructured":"Minist\u00e9rio da Sa\u00fadeS\u00e9rie hist\u00f3rica de acidentes por abelhas - 2000 a 2022"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02090","article-title":"Bee updated: current knowledge on bee venom and bee envenoming therapy","volume":"10","author":"Pucca","year":"2019","journal-title":"Front Immunol"},{"key":"B48","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1053\/j.ctsap.2006.10.002","article-title":"Hymenoptera stings","volume":"21","author":"Fitzgerald","year":"2006","journal-title":"Clin Tech Small Anim Pract"},{"key":"B49","unstructured":"Acidentes por abelhas \u2014 Minist\u00e9rio da Sa\u00fadeAcidentes por abelhas"},{"key":"B50","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.ibmb.2018.12.011","article-title":"Insect venom phospholipases A1 and A2: Roles in the envenoming process and allergy","volume":"105","author":"Perez-Riverol","year":"2019","journal-title":"Insect Biochem Mol Biol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22168371","article-title":"A review of honeybee venom allergens and allergenicity","volume":"22","author":"Burzy\u0144ska","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2222.1991.tb01659.x","article-title":"Emergency treatment of allergic reactions to Hymenoptera stings","volume":"21","author":"M\u00fcller","year":"1991","journal-title":"Clin Exp Allergy"},{"key":"B53","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/s13601-019-0292-5","article-title":"Risk factors for severe systemic sting reactions in wasp (Vespula spp.) and honeybee (Apis mellifera) venom allergic patients","volume":"9","author":"Fehr","year":"2019","journal-title":"Clin Transl Allergy"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01959","article-title":"Hymenoptera venom allergy: how does venom immunotherapy prevent anaphylaxis from bee and wasp stings","volume":"10","author":"Sahiner","year":"2019","journal-title":"Front Immunol"},{"key":"B55","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1590\/S0037-86822011000600020","article-title":"Africanized honeybee stings: how to treat them","volume":"44","author":"Ramb","year":"2011","journal-title":"Rev da Sociedade Bras Medicina Trop"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1590\/S0036-46652013000100011","article-title":"RRH: envenoming syndrome due to 200 stings from Africanized honeybees","volume":"55","author":"da Silva","year":"2013","journal-title":"Rev Inst Med Trop S Paulo"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1097\/PAF.0000000000000451","article-title":"A fatal case of acute renal failure from envenoming syndrome after massive bee attack: A case report and literature review","volume":"40","author":"Hughes","year":"2019","journal-title":"Am J Forensic Med Pathol"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.653151","article-title":"Single-arm, multicenter phase I\/II clinical trial for the treatment of envenomings by massive Africanized honey bee stings using the unique Apilic antivenom","volume":"12","author":"Barbosa","year":"2021","journal-title":"Front Immunol"},{"key":"B59","unstructured":"A pe\u00e7onha do escorpi\u00e3o Tityus serrulatus \u00e9 reconhecida por receptores de reconhecimento padr\u00e3o e induz ativa\u00e7\u00e3o celular e inflama\u00e7\u00e3o\n            ZoccalKF\n          10.11606\/T.60.2014.tde30102014-155349Ribeir\u00e3o Preto Faculdade Ci\u00eancias Farmac\u00eauticas Ribeir\u00e3o Preto2014"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1038\/227680a0","article-title":"Cleavage of structural proteins during the assembly of the head of bacteriophage T4","volume":"227","author":"Laemmli","year":"1970","journal-title":"Nature"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(81)90783-1","article-title":"Silver stain for proteins in polyacrylamide gels: a modified procedure with enhanced uniform sensitivity","volume":"117","author":"Morrissey","year":"1981","journal-title":"Anal Biochem"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0007017","article-title":"Naja annulifera Snake: New insights into the venom components and pathogenesis of envenomation","volume":"13","author":"Silva-de-Fran\u00e7a","year":"2019","journal-title":"PLoS Negl Trop Dis"},{"key":"B63","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/j.molimm.2016.06.004","article-title":"Sex matters: Systemic complement activity of female C57BL\/6J and BALB\/c J mice is limited by serum terminal pathway components","volume":"76","author":"Kotimaa","year":"2016","journal-title":"Mol Immunol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2004.11.016","article-title":"Functional analysis of the classical, alternative, and MBL pathways of the complement system: standardization and validation of a simple ELISA","volume":"296","author":"Seelen","year":"2005","journal-title":"J Immunol Methods"},{"key":"B65","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1111\/1467-8721.ep10768783","article-title":"Statistical power analysis","volume":"1","author":"Cohen","year":"1992","journal-title":"Curr Dir psychol Sci"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1125899","article-title":"Hyaluronan breakdown by snake venom hyaluronidases: From toxins delivery to immunopathology","volume":"14","author":"Silva de Fran\u00e7a","year":"2023","journal-title":"Front Immunol"},{"key":"B67","doi-asserted-by":"publisher","first-page":"79","DOI":"10.4269\/ajtmh.1990.43.79","article-title":"Quantity, analysis, and lethality of European and Africanized honeybee venoms","volume":"43","author":"Schumacher","year":"1990","journal-title":"Am J Trop Med Hyg"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12461","article-title":"Terminal complexes of the complement system: new structural insights and their relevance to function","volume":"274","author":"Morgan","year":"2016","journal-title":"Immunol Rev"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2017.06.009","article-title":"Molecular cell biology of complement membrane attack","volume":"72","author":"Morgan","year":"2017","journal-title":"Semin Cell Dev Biol"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/0091-6749(82)90045-8","article-title":"Complement activation by Hymenoptera venom allergenic extracts","volume":"70","author":"De Carolis","year":"1982","journal-title":"J Allergy Clin Immunol"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201300038","article-title":"Proteome and phosphoproteome of Africanized and European honeybee venoms","volume":"13","author":"Resende","year":"2013","journal-title":"Proteomics"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1067\/mai.2001.120013","article-title":"Antibody binding to venom carbohydrates is a frequent cause for double positivity to honeybee and yellow jacket venom in patients with stinging-insect allergy","volume":"108","author":"Hemmer","year":"2001","journal-title":"J Allergy Clin Immunol"},{"key":"B73","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1111\/imr.12468","article-title":"A journey through the lectin pathway of complement-MBL and beyond","volume":"274","author":"Garred","year":"2016","journal-title":"Immunol Rev"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1039765","article-title":"Distinction of early complement classical and lectin pathway activation via quantification of C1s\/C1-INH and MASP-1\/C1-INH complexes using novel ELISAs","volume":"13","author":"Hurler","year":"2022","journal-title":"Front Immunol"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1402838","article-title":"The levels of the lectin pathway serine protease MASP-1 and its complex formation with C1 inhibitor are linked to the severity of hereditary angioedema","volume":"195","author":"Hansen","year":"2015","journal-title":"J Immunol"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1016\/0041-0101(92)90875-6","article-title":"Rhabdomyonecrosis experimentally induced in Wistar rats by Africanized bee venom","volume":"30","author":"Azevedo-Marques","year":"1992","journal-title":"Toxicon"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2007.06.036","article-title":"Cytotoxicity of honeybee (Apis mellifera) venom in normal human lymphocytes and HL-60 cells","volume":"169","author":"Lee","year":"2007","journal-title":"Chem Biol Interact"},{"key":"B78","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1007\/s00430-021-00725-2","article-title":"Persistently elevated complement alternative pathway biomarkers in COVID-19 correlate with hypoxemia and predict in-hospital mortality","volume":"211","author":"Leatherdale","year":"2022","journal-title":"Med Microbiol Immunol"},{"key":"B79","doi-asserted-by":"publisher","first-page":"ib510","DOI":"10.1096\/fasebj.2019.33.1_supplement.lb510","article-title":"Anaphylatoxin C3a induces vasoconstriction and hypertension mediated by thromboxane A2 in mice","author":"Kerkovits","year":"2019","journal-title":"FASEB J"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.034600","article-title":"Functional relevance of the anaphylatoxin receptor C3aR for platelet function and arterial thrombus formation marks an intersection point between innate immunity and thrombosis","volume":"138","author":"Sauter","year":"2018","journal-title":"Circulation"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.31851","article-title":"Acute ischemic stroke post honeybee sting: A rare case report","volume":"14","author":"Kabra","year":"2022","journal-title":"Cureus"},{"key":"B82","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/01.shk.0000105502.75189.5e","article-title":"Role of C5a-C5aR interaction in sepsis","volume":"21","author":"Guo","year":"2004","journal-title":"Shock"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1172\/JCI163105","article-title":"C5aR1 signaling triggers lung immunopathology in COVID-19 through neutrophil extracellular traps","volume":"133","author":"Silva","year":"2023","journal-title":"J Clin Invest"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1096\/fj.15-271635","article-title":"Experimental design of complement component 5a-induced acute lung injury (C5a-ALI): a role of CC-chemokine receptor type 5 during immune activation by anaphylatoxin","volume":"29","author":"Russkamp","year":"2015","journal-title":"FASEB J"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.11.6921","article-title":"Platelet-activating factor and kinin-dependent vascular leakage as a novel functional activity of the soluble terminal complement complex","volume":"173","author":"Bossi","year":"2004","journal-title":"J Immunol"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14438","article-title":"Complement activation assessed by the plasma terminal complement complex and future risk of venous thromboembolism","volume":"17","author":"H\u00f8iland","year":"2019","journal-title":"J Thromb Haemost"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1463471\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T11:34:16Z","timestamp":1731497656000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1463471\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,13]]},"references-count":86,"alternative-id":["10.3389\/fimmu.2024.1463471"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1463471","relation":{},"ISSN":["1664-3224"],"issn-type":[{"type":"electronic","value":"1664-3224"}],"subject":[],"published":{"date-parts":[[2024,11,13]]},"article-number":"1463471"}}