{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:42:14Z","timestamp":1760146934929,"version":"build-2065373602"},"reference-count":53,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,21]],"date-time":"2024-12-21T00:00:00Z","timestamp":1734739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NIAID","award":["5R01AI125137","1R01AI121050","UG1OD024953","GM103427","GM139762"],"award-info":[{"award-number":["5R01AI125137","1R01AI121050","UG1OD024953","GM103427","GM139762"]}]},{"name":"Weitz Family Foundation","award":["5R01AI125137","1R01AI121050","UG1OD024953","GM103427","GM139762"],"award-info":[{"award-number":["5R01AI125137","1R01AI121050","UG1OD024953","GM103427","GM139762"]}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"publisher","award":["5R01AI125137","1R01AI121050","UG1OD024953","GM103427","GM139762"],"award-info":[{"award-number":["5R01AI125137","1R01AI121050","UG1OD024953","GM103427","GM139762"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute of General Medical Science (NIGMS)","award":["5R01AI125137","1R01AI121050","UG1OD024953","GM103427","GM139762"],"award-info":[{"award-number":["5R01AI125137","1R01AI121050","UG1OD024953","GM103427","GM139762"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) greatly complicates the treatment of skin and soft tissue infections (SSTI). It was previously found that subcutaneous (SQ) treatment with the mononuclear phagocyte (MP)-selective activator complement peptide-derived immunostimulant-02 (CPDI-02; formerly EP67) increases prophylaxis of outbred CD-1 mice against SQ infection with CA-MRSA. Here, we determined if treatment with CPDI-02 also increases curative protection. Methods: Female CD-1 mice were challenged SQ with CA-MRSA USA300 LAC, then CPDI-02 or inactive scCPDI-02 was administered by a topical, SQ, IM, or IV route at 6 or 24 h post-challenge. Abscess sizes were compared over 10 days and CA-MRSA burden, neutrophils, MP, and pro-inflammatory cytokines were compared in subcutaneous abscesses. CPDI-02 PK and distribution in female CD-1 mice were compared after IM or IV dosing and CPDI-02 toxicity in male and female CD-1 mice was determined by IM dose escalation and repeat IM dosing. Results: Repeat IM treatment starting at 6 h post-challenge decreased maximum abscess surface area, CA-MRSA burden, and time to resolution, whereas repeat treatment by a topical, SQ, or IV route had no effect. Repeat treatment starting at 24 h post-challenge was ineffective by the current routes. Single IM treatment starting at 6 h post-challenge was as effective as repeat IM treatment, increased systemic exposure to CPDI-02, and, in subcutaneous abscesses, initially decreased IL-1\u03b2 and increased MP. CPDI-02 was tolerated between 130 and 170 mg\/kg after IM dose escalation and between 65 and 130 mg\/kg after repeat IM dosing with males being more tolerant. Conclusions: Single early-stage IM treatment with CPDI-02 may increase curative protection against SSTI caused by CA-MRSA and\/or other pathogens controlled by activated MP.<\/jats:p>","DOI":"10.3390\/pharmaceutics16121621","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T04:33:29Z","timestamp":1734928409000},"page":"1621","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Early-Stage IM Treatment with the Host-Derived Immunostimulant CPDI-02 Increases Curative Protection of Healthy Outbred Mice Against Subcutaneous Infection with Community-Acquired Methicillin-Resistant Staphylococcus aureus USA300"],"prefix":"10.3390","volume":"16","author":[{"given":"Jason","family":"Stewart","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caleb","family":"Sandall","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob","family":"Parriott","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Curran","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Russell","family":"McCulloh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donald","family":"Ronning","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joy","family":"Phillips","sequence":"additional","affiliation":[{"name":"Biology Department, San Diego State University, San Diego, CA 92182, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin","family":"Schroeder","sequence":"additional","affiliation":[{"name":"Midwest Veterinary Services, Inc., Oakland, NE 68045, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christy","family":"Neel","sequence":"additional","affiliation":[{"name":"Midwest Veterinary Services, Inc., Oakland, NE 68045, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly","family":"Lechtenberg","sequence":"additional","affiliation":[{"name":"Midwest Veterinary Services, Inc., Oakland, NE 68045, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5047-0962","authenticated-orcid":false,"given":"Samuel","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology and the Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yazen","family":"Alnouti","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sohel","family":"Daria","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8956-9687","authenticated-orcid":false,"given":"D.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Creighton University, Omaha, NE 68178, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2446-9797","authenticated-orcid":false,"given":"Joseph","family":"Vetro","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA"},{"name":"Center for Drug Delivery and Nanomedicine, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S193","DOI":"10.1093\/cid\/ciz002","article-title":"Current Epidemiology, Etiology, and Burden of Acute Skin Infections in the United States","volume":"68","author":"Kaye","year":"2019","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1097\/QCO.0000000000000239","article-title":"Epidemiology and microbiology of skin and soft tissue infections","volume":"29","author":"Esposito","year":"2016","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_3","unstructured":"DiPiro, J.T., Yee, G.C., Haines, S.T., Nolin, T.D., Ellingrod, V.L., and Posey, L.M. (2023). Skin and Soft Tissue Infections. DiPiro\u2019s Pharmacotherapy: A Pathophysiologic Approach, McGraw Hill. [12th ed.]."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"ofae267","DOI":"10.1093\/ofid\/ofae267","article-title":"The Incidence of Skin and Soft Tissue Infections in the United States and Associated Healthcare Utilization Between 2010 and 2020","volume":"11","author":"Vella","year":"2024","journal-title":"Open Forum Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Xue, Y., Zhou, J., Xu, B.N., Li, Y., Bao, W., Cheng, X.L., He, Y., Xu, C.P., Ren, J., and Zheng, Y.R. (2022). Global Burden of Bacterial Skin Diseases: A Systematic Analysis Combined with Sociodemographic Index, 1990\u20132019. Front. Med., 9.","DOI":"10.3389\/fmed.2022.861115"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Linz, M.S., Mattappallil, A., Finkel, D., and Parker, D. (2023). Clinical Impact of Staphylococcus aureus Skin and Soft Tissue Infections. Antibiotics, 12.","DOI":"10.3390\/antibiotics12030557"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Gehrke, A.E., Giai, C., and Gomez, M.I. (2023). Staphylococcus aureus Adaptation to the Skin in Health and Persistent\/Recurrent Infections. Antibiotics, 12.","DOI":"10.3390\/antibiotics12101520"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Al Kindi, A., Alkahtani, A.M., Nalubega, M., El-Chami, C., O\u2019Neill, C., Arkwright, P.D., and Pennock, J.L. (2019). Staphylococcus aureus Internalized by Skin Keratinocytes Evade Antibiotic Killing. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.02242"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ray, G.T., Suaya, J.A., and Baxter, R. (2013). Incidence, microbiology, and patient characteristics of skin and soft-tissue infections in a U.S. population: A retrospective population-based study. BMC Infect. Dis., 13.","DOI":"10.1186\/1471-2334-13-252"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Mariani, F., and Galvan, E.M. (2023). Staphylococcus aureus in Polymicrobial Skinand Soft Tissue Infections: Impact of Inter-Species Interactionsin Disease Outcome. Antibiotics, 12.","DOI":"10.3390\/antibiotics12071164"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1016\/S0140-6736(06)68853-3","article-title":"Emergence and resurgence of meticillin-resistant Staphylococcus aureus as a public-health threat","volume":"368","author":"Grundmann","year":"2006","journal-title":"Lancet"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/S0140-6736(21)02724-0","article-title":"Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis","volume":"399","year":"2022","journal-title":"Lancet"},{"key":"ref_13","unstructured":"(2024). WHO Bacterial Priority Pathogens List, 2024: Bacterial Pathogens of Public Health Importance to Guide Research, Development and Strategies to Prevent and Control Antimicrobial Resistance, WHO."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/s41579-023-00852-y","article-title":"Staphylococcus aureus host interactions and adaptation","volume":"21","author":"Howden","year":"2023","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"adv00110","DOI":"10.2340\/00015555-3466","article-title":"Skin Infections Caused by Staphylococcus aureus","volume":"100","year":"2020","journal-title":"Acta Derm. Venereol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1038\/nrmicro2200","article-title":"Waves of resistance: Staphylococcus aureus in the antibiotic era","volume":"7","author":"Chambers","year":"2009","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_17","first-page":"135","article-title":"Penicillin\u2019s Discovery and Antibiotic Resistance: Lessons for the Future?","volume":"90","author":"Lobanovska","year":"2017","journal-title":"Yale J. Biol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"386","DOI":"10.3181\/00379727-51-13986","article-title":"Resistance of Staphylococcus aureus to the Action of Penicillin","volume":"51","author":"Rammelkamp","year":"1942","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1172\/JCI18535","article-title":"Antimicrobial resistance: The example of Staphylococcus aureus","volume":"111","author":"Lowy","year":"2003","journal-title":"J. Clin. Invest."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Gajdacs, M. (2019). The Continuing Threat of Methicillin-Resistant Staphylococcus aureus. Antibiotics, 8.","DOI":"10.3390\/antibiotics8020052"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/s13756-022-01146-3","article-title":"Use of broad-spectrum antimicrobials for more than 72 h and the detection of multidrug-resistant bacteria in Japanese intensive care units: A multicenter retrospective cohort study","volume":"11","author":"Yoshida","year":"2022","journal-title":"Antimicrob. Resist. Infect. Control"},{"key":"ref_22","unstructured":"CDC (2019). Antibiotic Resistance Threats in the United States, 2019."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.vaccine.2009.10.029","article-title":"Enhancement of in vivo and in vitro immune functions by a conformationally biased, response-selective agonist of human C5a: Implications for a novel adjuvant in vaccine design","volume":"28","author":"Morgan","year":"2009","journal-title":"Vaccine"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.vaccine.2011.10.054","article-title":"Control of methicillin resistant Staphylococcus aureus infection utilizing a novel immunostimulatory peptide","volume":"30","author":"Sheen","year":"2011","journal-title":"Vaccine"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1124\/pr.111.005223","article-title":"International Union of Basic and Clinical Pharmacology. [corrected]. LXXXVII. Complement peptide C5a, C4a, and C3a receptors","volume":"65","author":"Klos","year":"2013","journal-title":"Pharmacol. Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1021\/acsinfecdis.0c00005","article-title":"Targeted Amino Acid Substitution Overcomes Scale-Up Challenges with the Human C5a-Derived Decapeptide Immunostimulant EP67","volume":"6","author":"Alshammari","year":"2020","journal-title":"ACS Infect. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.ijpharm.2019.05.012","article-title":"Surface conjugation of EP67 to biodegradable nanoparticles increases the generation of long-lived mucosal and systemic memory T-cells by encapsulated protein vaccine after respiratory immunization and subsequent T-cell-mediated protection against respiratory infection","volume":"565","author":"Tallapaka","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1021\/acs.molpharmaceut.6b01088","article-title":"Encapsulation of an EP67-Conjugated CTL Peptide Vaccine in Nanoscale Biodegradable Particles Increases the Efficacy of Respiratory Immunization and Affects the Magnitude and Memory Subsets of Vaccine-Generated Mucosal and Systemic CD8+ T Cells in a Diameter-Dependent Manner","volume":"14","author":"Karuturi","year":"2017","journal-title":"Mol. Pharm."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.clim.2015.06.006","article-title":"Preliminary evidence that the novel host-derived immunostimulant EP67 can act as a mucosal adjuvant","volume":"161","author":"Karuturi","year":"2015","journal-title":"Clin. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.1021\/bc9002794","article-title":"Single-step conjugation of bioactive peptides to proteins via a self-contained succinimidyl bis-arylhydrazone","volume":"20","author":"Phillips","year":"2009","journal-title":"Bioconjug Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"8275","DOI":"10.1016\/j.vaccine.2010.10.008","article-title":"A novel adjuvant for vaccine development in the aged","volume":"28","author":"Morgan","year":"2010","journal-title":"Vaccine"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5904","DOI":"10.1016\/j.vaccine.2011.06.070","article-title":"Tumor-specific peptide-based vaccines containing the conformationally biased, response-selective C5a agonists EP54 and EP67 protect against aggressive large B cell lymphoma in a syngeneic murine model","volume":"29","author":"Kollessery","year":"2011","journal-title":"Vaccine"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4681","DOI":"10.1016\/j.vaccine.2012.04.084","article-title":"An agonist of human complement fragment C5a enhances vaccine immunity against Coccidioides infection","volume":"30","author":"Hung","year":"2012","journal-title":"Vaccine"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.4049\/jimmunol.158.3.1377","article-title":"Molecular adjuvant effects of a conformationally biased agonist of human C5a anaphylatoxin","volume":"158","author":"Tempero","year":"1997","journal-title":"J. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.smim.2016.03.014","article-title":"Monocyte-mediated defense against bacteria, fungi, and parasites","volume":"27","author":"Lauvau","year":"2015","journal-title":"Semin. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4259","DOI":"10.1016\/j.cell.2022.10.007","article-title":"Macrophages in health and disease","volume":"185","author":"Park","year":"2022","journal-title":"Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/s41577-022-00826-w","article-title":"Immune responses to human fungal pathogens and therapeutic prospects","volume":"23","author":"Lionakis","year":"2023","journal-title":"Nat. Rev. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1145513","DOI":"10.3389\/fpubh.2023.1145513","article-title":"The burden of skin and subcutaneous diseases: Findings from the global burden of disease study 2019","volume":"11","author":"Yakupu","year":"2023","journal-title":"Front Public Health"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1086\/533452","article-title":"Federal funding for the study of antimicrobial resistance in nosocomial pathogens: No ESKAPE","volume":"197","author":"Rice","year":"2008","journal-title":"J. Infect. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Vale de Macedo, G.H.R., Costa, G.D.E., Oliveira, E.R., Damasceno, G.V., Mendonca, J.S.P., Silva, L.D.S., Chagas, V.L., Bazan, J.M.N., Alianca, A., and Miranda, R.C.M. (2021). Interplay between ESKAPE Pathogens and Immunity in Skin Infections: An Overview of the Major Determinants of Virulence and Antibiotic Resistance. Pathogens, 10.","DOI":"10.3390\/pathogens10020148"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Pidwill, G.R., Gibson, J.F., Cole, J., Renshaw, S.A., and Foster, S.J. (2020). The Role of Macrophages in Staphylococcus aureus Infection. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.620339"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1093\/cid\/ciu444","article-title":"Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of America","volume":"59","author":"Stevens","year":"2014","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_43","first-page":"236","article-title":"Detection of secondary amines on solid phase","volume":"8","author":"Vojkovsky","year":"1995","journal-title":"Pept. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.ijantimicag.2019.07.014","article-title":"Eradication of meticillin-resistant Staphylococcus aureus from human skin by the novel LL-37-derived peptide P10 in four pharmaceutical ointments","volume":"54","author":"Nibbering","year":"2019","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.jim.2014.04.007","article-title":"Mouse models for infectious diseases caused by Staphylococcus aureus","volume":"410","author":"Kim","year":"2014","journal-title":"J. Immunol. Methods"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Shihan, M.H., Novo, S.G., Le Marchand, S.J., Wang, Y., and Duncan, M.K. (2021). A simple method for quantitating confocal fluorescent images. Biochem. Biophys. Rep., 25.","DOI":"10.1016\/j.bbrep.2021.100916"},{"key":"ref_47","unstructured":"Abbas, A.K., Lichtman, A.H., and Pillai, S. (2021). Cellular and Molecular Immunology E-Book, Elsevier Health Sciences."},{"key":"ref_48","unstructured":"Murphy, K.M., Weaver, C., and Berg, L.J. (2022). Janeway\u2019s Immunobiology, W.W. Norton & Company, Inc.. [10th ed.]."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1002\/JLB.4HI0918-346R","article-title":"Frontline Science: Staphylococcus aureus promotes receptor-interacting protein kinase 3- and protease-dependent production of IL-1beta in human neutrophils","volume":"105","author":"Kremserova","year":"2019","journal-title":"J. Leukoc. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Cho, J.S., Guo, Y., Ramos, R.I., Hebroni, F., Plaisier, S.B., Xuan, C., Granick, J.L., Matsushima, H., Takashima, A., and Iwakura, Y. (2012). Neutrophil-derived IL-1beta is sufficient for abscess formation in immunity against Staphylococcus aureus in mice. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1003047"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2818","DOI":"10.1111\/all.14413","article-title":"Mast cells and complement system: Ancient interactions between components of innate immunity","volume":"75","author":"Shafaghat","year":"2020","journal-title":"Allergy"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Palgan, K. (2023). Mast Cells and Basophils in IgE-Independent Anaphylaxis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241612802"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Mackey, E., and Moeser, A.J. (2022). Sex Differences in Mast Cell-Associated Disorders: A Life Span Perspective. Cold Spring Harb. Perspect. Biol., 14.","DOI":"10.1101\/cshperspect.a039172"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/16\/12\/1621\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:57:43Z","timestamp":1760115463000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/16\/12\/1621"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,21]]},"references-count":53,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["pharmaceutics16121621"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics16121621","relation":{},"ISSN":["1999-4923"],"issn-type":[{"type":"electronic","value":"1999-4923"}],"subject":[],"published":{"date-parts":[[2024,12,21]]}}}