Is Wheat Glutenin Extract Intrinsically Allergenic? Evaluation Using a Novel Adjuvant-Free Mouse Model of Systemic Anaphylaxis
Abstract
:1. Introduction
2. Results
2.1. Chronic Application of Wheat Glutenin (WG) onto Undamaged Skin Elicits Robust Specific IgE, and IgG1 Antibody Response in Balb/c Mice
2.2. Chronic Application of Wheat Glutenin (WG) onto Undamaged Skin also Elevates Total IgE Levels, Which Correlate with sIgE Levels
2.3. WG-Sensitized, but Not Vehicle-Sensitized Mice, Exhibit Life-Threatening Symptoms of Anaphylaxis upon Systemic Challenge with WG
2.4. Mice Experiencing Systemic Anaphylaxis Symptoms Following a Systemic Challenge with WG Displayed Pronounced Hypothermic Shock Responses (HSR)
2.5. Systemic Anaphylaxis Is also Linked to Substantial Mucosal Mast Cell Degranulation in This Model
2.6. Proteomic Analysis and Identification of Differentially Expressed Immune Biomarkers in the Spleen of Mice Undergoing Systemic Anaphylaxis
3. Discussion
4. Materials and Methods
4.1. Chemicals and Reagents
4.2. Mice Breeding and Establishment of a Plant-Protein-Free Mouse Colony
4.3. Preparation of Acid-Soluble Protein Extract from Wheat Flour
4.4. Skin Sensitization, Bleeding, and Plasma Sample Preparation
4.5. Elicitation of Systemic Anaphylaxis and Clinical Symptom Scoring
4.6. Determination of Hypothermic Shock Responses
4.7. Measurement of Specific IgE Antibody Levels
4.8. Measurement of Total Plasma IgE Concentration
4.9. Quantification of Mucosal Mast Cell Protease-1 (MMCP-1) Level
4.10. Spleen Extract Preparation and Proteomic Analysis of Immune Biomarkers
4.11. IgG1
4.12. IgE Cross-Reactivity
4.13. Statistics
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Biomarker | Control Mice (n = 5) | Anaphylactic Mice (n = 5) | Student’s t-Test p < |
---|---|---|---|
ACE | 38,316.3 ± 1853.51 | 91,252.75 ± 2471.8 | 0.001 |
CD27L | <40 (LOD) | 121.18 ± 18.33 | 0.005 |
CD30L | 7.57 ± 0.44 | 13.68 ± 0.67 | 0.001 |
Dtk | 1117.62 ± 26.36 | 1348.25 ± 46.15 | 0.005 |
IL-1a | 14.09 ± 2.34 | 25.88 ± 2.26 | 0.05 |
IL-1 R4 | 391.66 ± 114.88 | 1022.84 ± 20.13 | 0.005 |
IL-2 | 45.09 ± 1.4 | 75.5 ± 9.72 | 0.05 |
IL-6 | 59.98 ± 8.13 | 247.23 ± 26.76 | 0.001 |
IL-9 | 27.2 ± 4.86 | 124.92 ± 14.87 | 0.001 |
IL-12p70 | 33.78 ± 9.04 | 78.5 ± 11.13 | 0.05 |
IL-15 | 8185.98 ± 1532.53 | 25,061.06 ± 3151.03 | 0.005 |
IL-17E | 44.87 ± 19.9 | 191.72 ± 89.92 | 0.05 |
IL-23 | 273.89 ± 96.98 | 939.23 ± 164.11 | 0.05 |
MCSF | 80.09 ± 2.31 | 102.92 ± 3.43 | 0.001 |
MDC | 132.25 ± 5.29 | 198.63 ± 8.4 | 0.001 |
MIG | 280.49 ± 12.63 | 419.55 ± 6.13 | 0.001 |
MIP-1a | 78.61 ± 7.59 | 132.23 ± 2.6 | 0.001 |
MIP-1g | 943.39 ± 9.41 | 1001.9 ± 10.58 | 0.01 |
MIP-2 | 1.56 ± 0.76 | 4.65 ± 0.29 | 0.01 |
OPG | 299.86 ± 5.99 | 373.37 ± 22.5 | 0.05 |
PF4 | 27,562.44 ± 363.93 | 31,638.78 ± 629.49 | 0.001 |
Prolactin | 6.8 ± 1.27 | 16.57 ± 3.65 | 0.05 |
Resistin | 152.79 ± 11.04 | 1237.69 ± 38.04 | 0.001 |
SDF-1a | 161.28 ± 5.99 | 325.65 ± 14.87 | 0.001 |
VEGF | 253.17 ± 6.92 | 332.56 ± 6.53 | 0.001 |
VEGF R3 | <20 (LOD) | 410.16 ± 105.46 | 0.01 |
VEGF-D | 1.67 ± 0.57 | 39.8 ± 3.04 | 0.001 |
Biomarker | Control Mice (n = 5) | Anaphylactic Mice (n = 5) | Student’s t-Test p < |
---|---|---|---|
ALK-1 | 270.55 ± 10.48 | 134.18 ± 9.6 | 0.001 |
bFGF | 3828.16 ± 43.65 | 3255.51 ± 24.39 | 0.001 |
BLC | 5639.31 ± 124.83 | 4678.57 ± 44.06 | 0.001 |
CD40 | 4686.52 ± 208.06 | 3714.48 ± 242.08 | 0.05 |
CD40L | 3709.09 ± 69.08 | 2050.96 ± 74.63 | 0.001 |
CTLA4 | 887.48 ± 10.02 | 628.25 ± 9.38 | 0.001 |
Decorin | 14,941.56 ± 302.52 | 13,997.32 ± 180.47 | 0.05 |
Dkk-1 | 684.12 ± 27.13 | 521.43 ± 47.91 | 0.05 |
Eotaxin | 417.45 ± 3.96 | 184.63 ± 3.05 | 0.001 |
Fcg RIIB | 6800.55 ± 101.37 | 5598.51 ± 122.2 | 0.001 |
Flt-3L | 828.49 ± 8.84 | 559.04 ± 7.96 | 0.001 |
Galectin-1 | 6404.2 ± 235.85 | 5393.21 ± 164.45 | 0.05 |
Gas 1 | 1232.06 ± 66.89 | 974.73 ± 30.9 | 0.05 |
GITR | 9266.56 ± 301.11 | 7734.18 ± 336.51 | 0.05 |
HGF R | 768.41 ± 125.47 | 394.09 ± 80.25 | 0.05 |
IGFBP-2 | 408.43 ± 23.57 | 215.84 ± 36.66 | 0.005 |
IGFBP-3 | 2167.55 ± 64.32 | 1898.07 ± 38.67 | 0.05 |
IGFBP-6 | 1228.83 ± 77.13 | 541.13 ± 23.11 | 0.001 |
IL-1b | 14.15 ± 0.7 | 3.29 ± 0.63 | 0.001 |
IL-1ra | 618.95 ± 24.81 | 410.55 ± 14.05 | 0.001 |
IL-2 Ra | 810.79 ± 36.47 | 672 ± 26.15 | 0.05 |
IL-5 | 25.43 ± 3.36 | <6.8 (LOD) | 0.001 |
IL-12p40 | 12.32 ± 1.19 | 3.51 ± 0.91 | 0.001 |
IL-17 | 4.14 ± 0.67 | <2.4 (LOD) | 0.05 |
Leptin | 911.32 ± 76.19 | 626.32 ± 34.19 | 0.05 |
Leptin R | 136.2 ± 28.35 | 38.75 ± 6.82 | 0.05 |
LIX | 193.96 ± 2.38 | 149.09 ± 4.5 | 0.001 |
Lymphotactin | 9155.09 ± 515.92 | 3209.5 ± 663.09 | 0.001 |
MCP-5 | 144.37 ± 11.22 | 86.37 ± 11.55 | 0.05 |
MIP-3b | 23.78 ± 1.6 | 2.67 ± 0.78 | 0.001 |
OPN | 1870.22 ± 44.85 | 1329.38 ± 67.48 | 0.001 |
Pentraxin 3 | 376.37 ± 66.35 | 25.64 ± 4.36 | 0.005 |
SCF | 140.35 ± 3.85 | 58.14 ± 5.73 | 0.001 |
TNF RI | 919.47 ± 30.65 | 720.22 ± 21.12 | 0.005 |
TNFα | 53.92 ± 7.94 | 17.62 ± 5.1 | 0.01 |
TWEAK R | 2839.09 ± 90.38 | 224.95 ± 82.17 | 0.001 |
VEGF R1 | 436 ± 43.67 | 269.85 ± 13.02 | 0.05 |
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Jorgensen, R.; Gao, H.; Arul Arasan, T.S.; Van Antwerp, C.; Sundar, V.; Ng, P.K.W.; Gangur, V. Is Wheat Glutenin Extract Intrinsically Allergenic? Evaluation Using a Novel Adjuvant-Free Mouse Model of Systemic Anaphylaxis. Int. J. Mol. Sci. 2023, 24, 17247. https://doi.org/10.3390/ijms242417247
Jorgensen R, Gao H, Arul Arasan TS, Van Antwerp C, Sundar V, Ng PKW, Gangur V. Is Wheat Glutenin Extract Intrinsically Allergenic? Evaluation Using a Novel Adjuvant-Free Mouse Model of Systemic Anaphylaxis. International Journal of Molecular Sciences. 2023; 24(24):17247. https://doi.org/10.3390/ijms242417247
Chicago/Turabian StyleJorgensen, Rick, Haoran Gao, Tamil Selvan Arul Arasan, Chris Van Antwerp, Vaisheswini Sundar, Perry K. W. Ng, and Venu Gangur. 2023. "Is Wheat Glutenin Extract Intrinsically Allergenic? Evaluation Using a Novel Adjuvant-Free Mouse Model of Systemic Anaphylaxis" International Journal of Molecular Sciences 24, no. 24: 17247. https://doi.org/10.3390/ijms242417247