Systematic review of the subcutaneous air pouch model using monosodium urate and calcium pyrophosphate and recommendations for studying crystal-related arthropathies

Abstract

The subcutaneous air pouch model has been used extensively to study the pathophysiology of inflammatory conditions such as joint diseases and the potential efficacy of pharmacological treatments in vivo. Delivery of air between the subcutaneous and dermal layer of the intra-scapular zone of the rodent generates an environment analogous to the synovial joint space. Introduction of monosodium urate crystals or calcium pyrophosphate crystals into the air space produces a sterile acute inflammatory response mimicking clinical gout and pseudogout, respectively. The inflammatory response can be quantitatively and robustly evaluated by measuring leukocyte infiltration, inflammatory cytokine production, eicosanoid release, complement activation and reactive oxygen species generation. Despite the utility of this model, great variation exists within the literature regarding the design, sampling time points, and endpoints measured. This systematic review summarizes the current literature on the subcutaneous air pouch model studying monosodium urate or calcium pyrophosphate crystals and provides recommendations for standardizing and improving the reliability and validity of this model. Standardizing the experimental approach would improve inter-study comparability, increase the internal validity of studies and reproducibility of results, and ultimately improve the understanding of gout and pseudogout and accelerate the discovery of new pharmacological therapies.

Keywords

arthritis therapeutics / immunology / inflammatory mediators / joint injury / murine model / rheumatic and musculoskeletal disease

References

[1] Dalbeth N, Haskard DO. Mechanisms of inflammation in gout. Rheumatology. 2005; 44(9): 1090-1096.

[2] Schlesinger N. Management of acute and chronic gouty arthritis: present state-of-the-art. Drugs. 2004; 64(21): 2399-2416.

[3] Ragab G, Elshahaly M, Bardin T. Gout: an old disease in new perspective—a review. J Adv Res. 2017; 8(5): 495-511.

[4] Amiri F, Kolahi A-A, Nejadghaderi SA, et al. The burden of gout and its attributable risk factors in the Middle East and North Africa region, 1990 to 2019. J Rheumatol. 2023; 50(1): 107-116.

[5] Martillo MA, Nazzal L, Crittenden DB. The crystallization of monosodium urate. Curr Rheumatol Rep. 2013; 16(2): 400.

[6] Higgins PA. Gout and pseudogout. JAAPA. 2016; 29(3): 50-52.

[7] Campillo-Gimenez L, Renaudin F, Jalabert M, et al. Inflammatory potential of four different phases of calcium pyrophosphate relies on NF-κB activation and MAPK pathways. Front Immunol. 2018; 9: 2248.

[8] Hemstapat R, Duangiad P, Tangketsarawan B, et al. Improved polarized light microscopic detection of gouty crystals via dissolution with formalin and ethylenediamine tetraacetic acid. Sci Rep. 2023; 13(1): 7505.

[9] Shi Y, Mucsi AD, Ng G. Monosodium urate crystals in inflammation and immunity. Immunol Rev. 2010; 233(1): 203-217.

[10] FitzGerald JD, Dalbeth N, Mikuls T, et al. 2020 American College of Rheumatology guideline for the management of gout. Arthritis Care Res. 2020; 72(6): 744-760.

[11] Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006; 440(7081): 237-241.

[12] Cavalcanti NG, Marques CD, Lins ELTU, et al. Cytokine profile in gout: inflammation driven by IL-6 and IL-18? Immunol Investig. 2016; 45(5): 383-395.

[13] Busso N, So A. Mechanisms of inflammation in gout. Arthritis Res Ther. 2010; 12(2): 206.

[14] Shiels RG, Hewage W, Vidimce J, et al. Pharmacokinetics of bilirubin-10-sulfonate and biliverdin in the rat. Eur J Pharm Sci. 2021; 159: 105684.

[15] Russell IJ, Mansen C, Kolb LM, Kolb WP. Activation of the fifth component of human complement (C5) induced by monosodium urate crystals: C5 convertase assembly on the crystal surface. Clin Immunol Immunopathol. 1982; 24(2): 239-250.

[16] Ricklin D, Hajishengallis G, Yang K, Lambris JD. Complement: a key system for immune surveillance and homeostasis. Nat Immunol. 2010; 11(9): 785-797.

[17] So AK, Martinon F. Inflammation in gout: mechanisms and therapeutic targets. Nat Rev Rheumatol. 2017; 13(11): 639-647.

[18] Devi S, Stehlik C, Dorfleutner A. Protocol to create a murine subcutaneous air pouch for the study of monosodium urate crystal-induced gout. STAR Protoc. 2024; 5(1): 102888.

[19] Davies DE, Stevens AJ, Houston JB. Use of the rat air pouch model of inflammation to evaluate regional drug delivery. Agents Actions. 1992; 36: C109-C111.

[20] Franco-Molina MA, Santana-Krímskaya S, Rodríguez-Padilla C. Air pouch model: an alternative method for cancer drug discovery. In: Mehanna RA, ed. Cell Culture. IntechOpen; 2018.

[21] Selye H. On the mechanism through which hydrocortisone affects the resistance of tissues to injury; an experimental study with the granuloma pouch technique. JAMA. 1953; 152(13): 1207-1213.

[22] Generini S, Matucci-Cerinic M, Partsch G, et al. Evidence for hyaluronan production in the air pouch model in rats. Clin Exp Rheumatol. 2001; 19(3): 271-276.

[23] Duarte DB, Vasko MR, Fehrenbacher JC. Models of inflammation: carrageenan air pouch. Curr Protoc Pharmacol. 2012; 56(1): 5.6.1-5.6.8.

[24] Sedgwick AD, Sedgwick AD, Sedgwick AD, Sin YM, Sin YM. Increased inflammatory reactivity in newly formed lining tissue. J Pathol. 1983; 141(4): 483-495.

[25] Patil T, Soni A, Acharya S. A brief review on in vivo models for gouty arthritis. Metabol Open. 2021; 11: 100100.

[26] Marcotti A, Miralles A, Dominguez E, et al. Joint nociceptor nerve activity and pain in an animal model of acute gout and its modulation by intra-articular hyaluronan. Pain. 2018; 159(4): 739-748.

[27] Scanu A, Luisetto R, Oliviero F, et al. High-density lipoproteins inhibit urate crystal-induced inflammation in mice. Ann Rheum Dis. 2015; 74(3): 587-594.

[28] Hsu DZ, Chu PY, Chen SJ, Liu MY. Mast cell stabilizer ketotifen inhibits gouty inflammation in rats. Am J Ther. 2016; 23(4): e1009-15.

[29] Reber LL, Starkl P, Balbino B, et al. The tyrosine kinase inhibitor imatinib mesylate suppresses uric acid crystal-induced acute gouty arthritis in mice. PLoS One. 2017; 12(10): e0185704.

[30] Yang G, Yeon SH, Lee HE, et al. Suppression of NLRP3 inflammasome by oral treatment with sulforaphane alleviates acute gouty inflammation. Rheumatology. 2018; 57(4): 727-736.

[31] Moilanen LJ, Hämäläinen M, Lehtimäki L, Nieminen RM, Moilanen E. Urate crystal induced inflammation and joint pain are reduced in transient receptor potential ankyrin 1 deficient mice--potential role for transient receptor potential ankyrin 1 in gout. PLoS One. 2015; 10(2): e0117770.

[32] Lee HE, Yang G, Kim ND, et al. Targeting ASC in NLRP3 inflammasome by caffeic acid phenethyl ester: a novel strategy to treat acute gout. Sci Rep. 2016; 6(1): 38622.

[33] Hsu D-Z, Chen S-J, Chu P-Y, Liu M-Y. Therapeutic effects of sesame oil on monosodium urate crystal-induced acute inflammatory response in rats. Springerplus. 2013; 2(1): 659.

[34] Wang Y, Viollet B, Terkeltaub R, Liu-Bryan R. AMP-activated protein kinase suppresses urate crystal-induced inflammation and transduces colchicine effects in macrophages. Ann Rheum Dis. 2016; 75: 286-294.

[35] Della Beffa C, Klawonn F, Menetski JP, Schumacher HR, Pessler F. Evaluation of glyceraldehyde-3-phosphate, prolylpeptidyl isomerase a, and a set of stably expressed genes as reference mRNAs in urate crystal inflammation. BMC Res Notes. 2011; 4: 443.

[36] Yang QB, Li LQ, Zhang QB, He YL, Mi QS, Zhou JG. MicroRNA-223 deficiency exacerbates acute inflammatory response to monosodium urate crystals by targeting NLRP3. J Inflamm Res. 2021; 14: 1845-1858.

[37] Choi N, Yang G, Jang JH, et al. Loganin alleviates gout inflammation by suppressing NLRP3 inflammasome activation and mitochondrial damage. Molecules. 2021; 26(4): 1071.

[38] Wang X, Chi J, Dong B, et al. MiR-223-3p and miR-22-3p inhibit monosodium urate-induced gouty inflammation by targeting NLRP3. Int J Rheum Dis. 2021; 24(4): 599-607.

[39] Stubelius A, Sheng W, Lee S, Olejniczak J, Guma M, Almutairi A. Disease-triggered drug release effectively prevents acute inflammatory flare-ups, achieving reduced dosing. Small. 2018; 14(32): e1800703.

[40] Gupta M, Wani A, Ahsan AU, et al. Safranal inhibits NLRP3 inflammasome activation by preventing ASC oligomerization. Toxicol Appl Pharmacol. 2021; 423: 115582.

[41] Huang JH, Chiang BL. Regulatory T cells induced by B cells suppress NLRP3 inflammasome activation and alleviate monosodium urate-induced gouty inflammation. iScience. 2021; 24(2): 102103.

[42] Pan Y-G, Huang M-T, Sekar P, Huang D-Y, Lin W-W, Hsieh S-L. Decoy receptor 3 inhibits monosodium urate-induced NLRP3 inflammasome activation via reduction of reactive oxygen species production and lysosomal rupture. Front Immunol. 2021; 12: 392.

[43] Ali M, Gupta M, Wani A, et al. IIIM-941, a stilbene derivative inhibits NLRP3 inflammasome activation by inducing autophagy. Front Pharmacol. 2021; 12(1612): 695712.

[44] Huang S, Wang Y, Lin S, Guan W, Liang H, Shen J. Neutrophil autophagy induced by monosodium urate crystals facilitates neutrophil extracellular traps formation and inflammation remission in gouty arthritis. Front Endocrinol. 2023; 14: 1071630.

[45] Yan F, Zhang H, Yuan X, et al. Comparison of the different monosodium urate crystals in the preparation process and pro-inflammation. Adv Rheumatol. 2023; 63: 39.

[46] Bai L, Wu C, Lei S, et al. Potential anti-gout properties of Wuwei Shexiang pills based on network pharmacology and pharmacological verification. J Ethnopharmacol. 2023; 305: 116147.

[47] Liu-Bryan R, Scott P, Sydlaske A, Rose DM, Terkeltaub R. Innate immunity conferred by toll-like receptors 2 and 4 and myeloid differentiation factor 88 expression is pivotal to monosodium urate monohydrate crystal-induced inflammation. Arthritis Rheum. 2005; 52(9): 2936-2946.

[48] Murakami Y, Akahoshi T, Hayashi I, et al. Inhibition of monosodium urate monohydrate crystal-induced acute inflammation by retrovirally transfected prostaglandin D synthase. Arthritis Rheum. 2003; 48(10): 2931-2941.

[49] Inokuchi T, Moriwaki Y, Tsutsui H, et al. Plasma interleukin (IL)-18 (interferon-gamma-inducing factor) and other inflammatory cytokines in patients with gouty arthritis and monosodium urate monohydrate crystal-induced secretion of IL-18. Cytokine. 2006; 33: 21-27.

[50] Hoffman HM, Scott P, Mueller JL, et al. Role of the leucine-rich repeat domain of cryopyrin/NALP3 in monosodium urate crystal-induced inflammation in mice. Arthritis Rheumatol. 2010; 62(7): 2170-2179.

[51] Jung SM, Schumacher HR, Kim H, Kim M, Lee SH, Pessler F. Reduction of urate crystal-induced inflammation by root extracts from traditional oriental medicinal plants: elevation of prostaglandin D2 levels. Arthritis Res Ther. 2007; 9(4): R64.

[52] Scott P, Ma H, Viriyakosol S, Terkeltaub R, Liu-Bryan R. Engagement of CD14 mediates the inflammatory potential of monosodium urate crystals. J Immunol. 2006; 177(9): 6370-6378.

[53] Kotiw M, Morgan M, Taylor SM, Shiels IA. Detection of anti-TNFalpha activity in canine hyperimmune serum using a TNFalpha inhibition assay. Vet Clin Pathol. 2010; 39: 46-52.

[54] Mohapatra A, Rajendrakumar SK, Chandrasekaran G, et al. Biomineralized nanoscavenger abrogates proinflammatory macrophage polarization and induces neutrophil clearance through reverse migration during gouty arthritis. ACS Appl Mater Interfaces. 2023; 15(3): 3812-3825.

[55] Nalbant S, Akmaz I, Kaplan M, Avsar K, Solmazgul E, Sahan B. Does rofecoxib increase TNF-alpha levels? Clin Exp Rheumatol. 2006; 24(4): 361-365.

[56] Shiels RG, Hewage W, Pennell EN, et al. Biliverdin and bilirubin sulfonate inhibit monosodium urate induced sterile inflammation in the rat. Eur J Pharm Sci. 2020; 155: 105546.

[57] Ferrari AJ, Van Linthoudt D, Morrone L, Branigan P, Schumacher HR, Baker DG. Nonsteroidal anti-inflammatory drugs and prostaglandins: their interactions and effects on the particulate-induced inflammatory process implicated in joint implant-loosening and on monosodium urate crystal-induced inflammation. Am J Ther. 1996; 3(3): 189-194.

[58] Ryckman C, McColl SR, Vandal K, et al. Role of S100A8 and S100A9 in neutrophil recruitment in response to monosodium urate monohydrate crystals in the air-pouch model of acute gouty arthritis. Arthritis Rheum. 2003; 48(8): 2310-2320.

[59] Forrest MJ, Zammit V, Brooks PM. Inhibition of leucotriene B4 synthesis by BW 755c does not reduce polymorphonuclear leucocyte (PMNL) accumulation induced by monosodium urate crystals. Ann Rheum Dis. 1988; 47(3): 241-246.

[60] Kumagai Y, Watanabe W, Kobayashi A, Sato K, Onuma S, Sakamoto H. Inhibitory effect of low density lipoprotein on the inflammation-inducing activity of calcium pyrophosphate dihydrate crystals. J Rheumatol. 2001; 28(12): 2674-2680.

[61] Brooks PM, Burton D, Forrest MJ. Crystal-induced inflammation in the rat subcutaneous air-pouch. Br J Pharmacol. 1987; 90(2): 413-419.

[62] Tate GA, Mandell BF, Karmali RA, et al. Suppression of monosodium urate crystal-induced acute inflammation by diets enriched with gamma-linolenic acid and eicosapentaenoic acid. Arthritis Rheum. 1988; 31(12): 1543-1551.

[63] Gordon TP, Clifton P, James MJ, Roberts-Thomson PJ. Lack of correlation between in vitro and in vivo effects of low density lipoprotein on the inflammatory activity of monosodium urate crystals. Ann Rheum Dis. 1986; 45(8): 673-676.

[64] Schiltz C, Liote F, Prudhommeaux F, et al. Monosodium urate monohydrate crystal-induced inflammation in vivo: quantitative histomorphometric analysis of cellular events. Arthritis Rheum. 2002; 46(6): 1643-1650.

[65] Fam AG, Schumacher HR, Clayburne G, et al. A comparison of five preparations of synthetic monosodium urate monohydrate crystals. J Rheumatol. 1992; 19(5): 780-787.

[66] Ortiz-Bravo E, Sieck MS, Schumacher HR. Changes in the proteins coating monosodium urate crystals during active and subsiding inflammation. Immunogold studies of synovial fluid from patients with gout and of fluid obtained using the rat subcutaneous air pouch model. Arthritis Rheum. 1993; 36(9): 1274-1285.

[67] Pang L, Hayes CP, Buac K, Yoo D-g, Rada B. Pseudogout-associated inflammatory calcium pyrophosphate dihydrate microcrystals induce formation of neutrophil extracellular traps. J Immunol. 2013; 190(12): 6488-6500.

[68] Torres R, Macdonald L, Croll SD, et al. Hyperalgesia, synovitis and multiple biomarkers of inflammation are suppressed by interleukin 1 inhibition in a novel animal model of gouty arthritis. Ann Rheum Dis. 2009; 68(10): 1602-1608.

[69] Akahoshi T, Namai R, Murakami Y, et al. Rapid induction of peroxisome proliferator-activated receptor γ expression in human monocytes by monosodium urate monohydrate crystals. Arthritis Rheumatol. 2003; 48(1): 231-239.

[70] Chiu CW, Chen HM, Wu TT, et al. Differential proteomics of monosodium urate crystals-induced inflammatory response in dissected murine air pouch membranes by iTRAQ technology. Proteomics. 2015; 15(19): 3338-3348.

[71] Zhang Y, Lee SYC, Zhang Y, Furst D, Fitzgerald J, Ozcan A. Wide-field imaging of birefringent synovial fluid crystals using lens-free polarized microscopy for gout diagnosis. Sci Rep. 2016; 6: 28793.

[72] Sin YM, Sedgwick AD, Moore A, Willoughby DA. Studies on the clearance of calcium pyrophosphate crystals from facsimile synovium. Ann Rheum Dis. 1984; 43(3): 487-492.

[73] Yang QB, Zhang MY, Yang L, Wang J, Mi QS, Zhou JG. Deficiency of histone deacetylases 3 in macrophage alleviates monosodium urate crystals-induced gouty inflammation in mice. Arthritis Res Ther. 2024; 26(1): 96.

[74] Rull M, Clayburne G, Sieck M, Schumacher HR. Intra-articular corticosteroid preparations: different characteristics and their effect during inflammation induced by monosodium urate crystals in the rat subcutaneous air pouch. Rheumatology. 2003; 42(9): 1093-1100.

[75] Yang Q-B, He Y-L, Zhang Q-B, Mi Q-S, Zhou J-G. Downregulation of transcription factor T-bet as a protective strategy in monosodium urate-induced gouty inflammation. Front Immunol. 2019; 10: 1199.

[76] Yang Q, Zhang Q, Qing Y, Zhou L, Mi Q, Zhou J. miR-155 is dispensable in monosodium urate-induced gouty inflammation in mice. Arthritis Res Ther. 2018; 20(1): 144.

[77] Wang J, Yang Q, Zhang Q, et al. Invariant natural killer T cells ameliorate monosodium urate crystal-induced gouty inflammation in mice. Front Immunol. 2017; 8(1): 1710.

[78] Singh HP, Tiwary AK, Jain S. Preparation and in vitro, in vivo characterization of elastic liposomes encapsulating cyclodextrin-colchicine complexes for topical delivery of colchicine. Yakugaku Zasshi. 2010; 130(3): 397-407.

[79] Singh HP, Utreja P, Tiwary AK, Jain S. Elastic liposomal formulation for sustained delivery of colchicine: in vitro characterization and in vivo evaluation of anti-gout activity. AAPS J. 2009; 11: 54-64.

[80] Ye SM, Zhou MZ, Jiang WJ, et al. Silencing of gasdermin D by siRNA-loaded PEI-Chol lipopolymers potently relieves acute gouty arthritis through inhibiting pyroptosis. Mol Pharm. 2021; 18(2): 667-678.

[81] Liote F, Prudhommeaux F, Schiltz C, et al. Inhibition and prevention of monosodium urate monohydrate crystal-induced acute inflammation in vivo by transforming growth factor beta1. Arthritis Rheum. 1996; 39(7): 1192-1198.

[82] McWherter C, Choi Y-J, Serrano RL, Mahata SK, Terkeltaub R, Liu-Bryan R. Arhalofenate acid inhibits monosodium urate crystal-induced inflammatory responses through activation of AMP-activated protein kinase (AMPK) signaling. Arthritis Res Ther. 2018; 20: 204.

[83] Rossetti RG, Brathwaite K, Zurier RB. Suppression of acute inflammation with liposome associated prostaglandin E1. Prostaglandins. 1994; 48(3): 187-195.

[84] Paré G, Vitry J, Marceau F, et al. The development of a targeted and more potent, anti-inflammatory derivative of colchicine: implications for gout. Biochem Pharmacol. 2020; 180: 114125.

[85] Qiao C-Y, Li Y, Shang Y, et al. Management of gout-associated MSU crystals-induced NLRP3 inflammasome activation by procyanidin B2: targeting IL-1β and cathepsin B in macrophages. Inflammopharmacology. 2020; 28(6): 1481-1493.

[86] Terkeltaub R, Baird S, Sears P, Santiago R, Boisvert W. The murine homolog of the interleukin-8 receptor CXCR-2 is essential for the occurrence of neutrophilic inflammation in the air pouch model of acute urate crystal-induced gouty synovitis. Arthritis Rheum. 1998; 41(5): 900-909.

[87] Ponce L, Arjona M, Blanco G, et al. The effect of montelukast in a model of gouty arthritis induced by sodium monourate crystals. Investig Clin. 2011; 52: 15-22.

[88] Yao X, Ding Z, Xia Y, et al. Inhibition of monosodium urate crystal-induced inflammation by scopoletin and underlying mechanisms. Int Immunopharmacol. 2012; 14(4): 454-462.

[89] Desai J, Foresto-Neto O, Honarpisheh M, et al. Particles of different sizes and shapes induce neutrophil necroptosis followed by the release of neutrophil extracellular trap-like chromatin. Sci Rep. 2017; 7: 15003.

[90] Uratsuji H, Tada Y, Kawashima T, et al. P2Y6 receptor signaling pathway mediates inflammatory responses induced by monosodium urate crystals. J Immunol. 2012; 188: 436-444.

[91] Pessler F, Mayer CT, Jung SM, et al. Identification of novel monosodium urate crystal regulated mRNAs by transcript profiling of dissected murine air pouch membranes. Arthritis Res Ther. 2008; 10(3): R64.

[92] Rainer TH, Cheng CH, Janssens HJ, et al. Oral prednisolone in the treatment of acute gout: a pragmatic, multicenter, double-blind, randomized trial. Ann Intern Med. 2016; 164(7): 464-471.

[93] Iverson C, Bacong A, Liu S, et al. Omega-3-carboxylic acids provide efficacious anti-inflammatory activity in models of crystal-mediated inflammation. Sci Rep. 2018; 8: 1217.

[94] Zhang T, Wang G, Zheng J, Li S, Xu J. Profile of serum cytokine concentrations in patients with gouty arthritis. J Int Med Res. 2021; 49(11): 3000605211055618.

[95] Halperin Kuhns VL, Woodward OM. Sex differences in urate handling. Int J Mol Sci. 2020; 21(12): 4269.

[96] Lee J, Sumpter N, Merriman TR, Liu-Bryan R, Terkeltaub R. The evolving landscape of gout in the female: a narrative review. Gout Urate Cryst Deposition Dis. 2024; 2(1): 1-16.

[97] Kosyreva AM, Makarova OV, Kakturskiy LV, Mikhailova LP, Boltovskaya MN, Rogov KA. Sex differences of inflammation in target organs, induced by intraperitoneal injection of lipopolysaccharide, depend on its dose. J Inflamm Res. 2018; 11: 431-445.

[98] Spalinger MR, Scharl M. Mono sodium urate crystal-induced peritonitis for in vivoAssessment of inflammasome activation. Bio Protoc. 2018; 8(5): e2754.

[99] Pineda C, Fuentes-Gómez AJ, Hernández-Díaz C, et al. Animal model of acute gout reproduces the inflammatory and ultrasonographic joint changes of human gout. Arthritis Res Ther. 2015; 17(1): 37.

[100] Mariotte A, De Cauwer A, Po C, et al. A mouse model of MSU-induced acute inflammation in vivo suggests imiquimod-dependent targeting of Il-1β as relevant therapy for gout patients. Theranostics. 2020; 10(5): 2158-2171.

[101] Lu J, Hou X, Yuan X, et al. Knockout of the urate oxidase gene provides a stable mouse model of hyperuricemia associated with metabolic disorders. Kidney Int. 2018; 93(1): 69-80.

[102] Christensen AD, Haase C, Cook AD, Hamilton JA. K/BxN serum-transfer arthritis as a model for human inflammatory arthritis. Front Immunol. 2016; 7: 213.

[103] Fehrenbacher JC, McCarson KE. Models of inflammation: carrageenan air pouch. Curr Protoc. 2021; 1(8): e183.

[104] Brand DD, Latham KA, Rosloniec EF. Collagen-induced arthritis. Nat Protoc. 2007; 2(5): 1269-1275.

[105] Barth CR, Funchal GA, Luft C, de Oliveira JR, Porto BN, Donadio MV. Carrageenan-induced inflammation promotes ROS generation and neutrophil extracellular trap formation in a mouse model of peritonitis. Eur J Immunol. 2016; 46(4): 964-970.

RIGHTS & PERMISSIONS

2025 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.