Skip to main content
SpringerLink
Log in

Transcriptomic Analysis of Circulating Neutrophils in Sheep with Mineral Element Imbalance

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

This experiment was designed to investigate the effects of mineral element imbalance on gene transcription in peripheral circulating neutrophils of sheep. Ten female sheep weighing 30 kg of similar age and physiological condition were randomly selected and injected via central venous catheterization with EDTA at a concentration of 4% (W/V) to construct a model of mineral element imbalance. As self-control, the sheep were divided into control [Con, before EDTA injection, time point 0 (T0)], EDTA [12 h after EDTA injection, time point 12 h (T12h)] and recovery [HF, 7 days after injection, time point 7 days (T7d)] groups. Whole blood was collected, and serum and neutrophils were separated for ionomic and transcriptomic analysis. The results showed that levels of P (P < 0.05), Zn (P < 0.01), K (P < 0.01) and some other elements were significantly lower in sheep in the EDTA group than in those in the control group, but levels of P (P > 0.05), Zn (P > 0.05) and K (P > 0.05) were similar in the recovery and control groups. Levels of Ca (P > 0.05) and Cu (P < 0.05) were higher after injection, and levels of Cu (P < 0.01) continued to increase during the recovery period. There were 1561 genes, including S100 family genes, significantly differentially expressed in neutrophils between the control and trial groups, and these genes were mainly enriched in the categories defense response, immune response, regulation of interleukin production and other functions. The top enriched signaling pathways were phagosome, NF-κB and Toll-like receptor. Mineral element homeostasis imbalance affected the gene transcriptome of circulating neutrophils, demonstrating the importance of carefully controlling the addition of mineral elements.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Sordillo LM, Raphael W (2013) Significance of metabolic stress, lipid mobilization, and inflammation on transition cow disorders. Vet Clin North Am Food Anim Pract 29(2):267–278

    Article  PubMed  Google Scholar 

  2. Spears JW, Weiss WP (2008) Role of antioxidants and trace elements in health and immunity of transition dairy cows. Vet J 176(1):70–76

    Article  CAS  PubMed  Google Scholar 

  3. Rinaldi M, Moroni P, Paape MJ, Bannerman DD (2008) Differential alterations in the ability of bovine neutrophils to generate extracellular and intracellular reactive oxygen species during the periparturient period. Vet J 178(2):208–213

    Article  CAS  PubMed  Google Scholar 

  4. Overton TR, Yasui T (2014) Practical applications of trace minerals for dairy cattle. J Anim Sci 92(2):416–426

    Article  CAS  PubMed  Google Scholar 

  5. Batistel F, Osorio JS, Tariq MR, Li C, Caputo J, Socha MT, Loor JJ (2017) Peripheral leukocyte and endometrium molecular biomarkers of inflammation and oxidative stress are altered in peripartal dairy cows supplemented with Zn, Mn, and Cu from amino acid complexes and Co from Co glucoheptonate. J Anim Sci Biotechnol 8(4):885–896

    Google Scholar 

  6. Wessels I, Pupke JT, von Trotha KT, Gombert A, Himmelsbach A, Fischer HJ, Jacobs MJ, Rink L, Grommes J (2020) Zinc supplementation ameliorates lung injury by reducing neutrophil recruitment and activity. Thorax 75(3):253–261

    Article  PubMed  Google Scholar 

  7. Wahab A, Mushtaq K, Borak SG, Bellam N (2020) Zinc-induced copper deficiency, sideroblastic anemia, and neutropenia: a perplexing facet of zinc excess. Clin Case Rep 8(9):1666–1671

    Article  PubMed  PubMed Central  Google Scholar 

  8. Amundson LA, Rowson AD, Crump PM, Prichard AP, Cheng AA, Wimmler CE, Klister M, Weaver SR, Bascom SS, Nuzback DE et al (2018) Effect of induced hypocalcemia in nonlactating, nonpregnant Holstein cows fed negative DCAD with low, medium, or high concentrations of calcium. J Anim Sci 96(12):5010–5023

    Article  PubMed  PubMed Central  Google Scholar 

  9. Ao T, Pierce JL, Power R, Pescatore AJ, Cantor AH, Dawson KA, Ford MJ (2009) Effects of feeding different forms of zinc and copper on the performance and tissue mineral content of chicks. Poult Sci 88(10):2171–2175

    Article  CAS  PubMed  Google Scholar 

  10. Hill GM, Shannon MC (2019) Copper and zinc nutritional issues for agricultural animal production. Biol Trace Elem Res 188(1):148–159

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hu X, Sheikhahmadi A, Li X, Wang Y, Jiao H, Lin H, Zhang B, Song Z (2016) Effect of zinc on appetite regulatory peptides in the hypothalamus of salmonella-challenged broiler chickens. Biol Trace Elem Res 172(1):228–233

    Article  CAS  PubMed  Google Scholar 

  12. Guo Q, Zhao Y, Li J, Liu J, Yang X, Guo X, Kuang M, Xia H, Zhang Z, Cao L et al (2021) Induction of alarmin S100A8/A9 mediates activation of aberrant neutrophils in the pathogenesis of COVID-19. Cell Host Microbe 29(2):222-235 e224

    Article  CAS  PubMed  Google Scholar 

  13. Ometto F, Friso L, Astorri D, Botsios C, Raffeiner B, Punzi L, Doria A (2017) Calprotectin in rheumatic diseases. Exp Biol Med (Maywood) 242(8):859–873

    Article  CAS  Google Scholar 

  14. Wang S, Song R, Wang Z, Jing Z, Wang S, Ma J (2018) S100A8/A9 in inflammation. Front Immunol 9:1298

    Article  PubMed  PubMed Central  Google Scholar 

  15. Holzinger D, Nippe N, Vogl T, Marketon K, Mysore V, Weinhage T, Dalbeth N, Pool B, Merriman T, Baeten D et al (2014) Myeloid-related proteins 8 and 14 contribute to monosodium urate monohydrate crystal-induced inflammation in gout. Arthritis Rheumatol 66(5):1327–1339

    Article  CAS  PubMed  Google Scholar 

  16. Zhang Z, Han N, Shen Y (2020) S100A12 promotes inflammation and cell apoptosis in sepsis-induced ARDS via activation of NLRP3 inflammasome signaling. Mol Immunol 122:38–48

    Article  CAS  PubMed  Google Scholar 

  17. Lee DG, Woo JW, Kwok SK, Cho ML, Park SH (2013) MRP8 promotes Th17 differentiation via upregulation of IL-6 production by fibroblast-like synoviocytes in rheumatoid arthritis. Exp Mol Med 45(4):e20

    Article  PubMed  PubMed Central  Google Scholar 

  18. Kang KY, Woo JW, Park SH (2014) S100A8/A9 as a biomarker for synovial inflammation and joint damage in patients with rheumatoid arthritis. Korean J Intern Med 29(1):12–19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Sorci G, Riuzzi F, Giambanco I, Donato R (2013) RAGE in tissue homeostasis, repair and regeneration. Biochim Biophys Acta 1833(1):101–109

    Article  CAS  PubMed  Google Scholar 

  20. Yang Z, Yan WX, Cai H, Tedla N, Armishaw C, Di Girolamo N, Wang HW, Hampartzoumian T, Simpson JL, Gibson PG et al (2007) S100A12 provokes mast cell activation: a potential amplification pathway in asthma and innate immunity. J Allergy Clin Immunol 119(1):106–114

    Article  CAS  PubMed  Google Scholar 

  21. Kozlyuk N, Monteith AJ, Garcia V, Damo SM, Skaar EP, Chazin WJ (2019) S100 Proteins in the Innate Immune Response to Pathogens. Methods Mol Biol 1929:275–290

  22. Zackular JP, Chazin WJ, Skaar EP (2015) Nutritional immunity: S100 proteins at the host-pathogen interface. J Biol Chem 290(31):18991–18998

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Gilston BA, Skaar EP, Chazin WJ (2016) Binding of transition metals to S100 proteins. Sci China Life Sci 59(8):792–801

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Cai Z, Xie Q, Hu T, Yao Q, Zhao J, Wu Q, Tang Q (2020) S100A8/A9 in myocardial infarction: a promising biomarker and therapeutic target. Front Cell Dev Biol 8:603902

    Article  PubMed  PubMed Central  Google Scholar 

  25. Nikolakopoulou Z, Hector LR, Creagh-Brown BC, Evans TW, Quinlan GJ, Burke-Gaffney A (2019) Plasma S100A8/A9 heterodimer is an early prognostic marker of acute kidney injury associated with cardiac surgery. Biomark Med 13(3):205–218

    Article  CAS  PubMed  Google Scholar 

  26. Okada K, Okabe M, Kimura Y, Itoh H, Ikemoto M (2019) Serum S100A8/A9 as a potentially sensitive biomarker for inflammatory bowel disease. Lab Med 50(4):370–380

    Article  PubMed  Google Scholar 

  27. van de Logt F, Day AS (2013) S100A12: a noninvasive marker of inflammation in inflammatory bowel disease. J Dig Dis 14(2):62–67

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank all the assistance from the Heilongjiang Provincial Key Laboratory of Prevention and Control of Bovine Diseases throughout the study.

Funding

This work was supported by the National Key Research and Development Program (2016YFD0501203) and Heilongjiang Bayi Agricultural University Support Program for San Heng San Zong (TDJH201903).

Author information

Authors and Affiliations

  1. College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, No. 5 Xinfeng Road, Daqing, 163319, People’s Republic of China

    Di Wang, Ming Ji, Qijun Zhou, Shuai Lian, Jianfa Wang, Jiasan Zheng & Rui Wu

  2. Suihua Center for Animal Disease Control and Prevention, Xiushui Jiayuan, North Yellow River Road, North Forest District, Suihua, 152000, People’s Republic of China

    Chengyuan Su

Authors
  1. Di Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ming Ji
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qijun Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chengyuan Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shuai Lian
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jianfa Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jiasan Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rui Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

D.W. wrote the main manuscript text, M.J and Q.Z prepared Figs. 1 and 2, C.S and S.L prepared Figs. 3, 4, 5, 6, and 7, J.W,W.R and J.Z review and editing the main manuscript text. All authors reviewed the manuscript.

Corresponding authors

Correspondence to Jiasan Zheng or Rui Wu.

Ethics declarations

Ethics approval and consent to participate

The study was conducted in compliance with the ARRIVE guidelines, and approved by the Ethics Committee of Heilongjiang Bayi Agri-cultural University (BYAU20200602, 2020.06). Consent was written informed from the owner of the animals.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, D., Ji, M., Zhou, Q. et al. Transcriptomic Analysis of Circulating Neutrophils in Sheep with Mineral Element Imbalance. Biol Trace Elem Res 200, 2135–2146 (2022). https://doi.org/10.1007/s12011-021-02869-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-021-02869-x

Keyword

Search

Navigation