Research Article
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Demir eksikliği anemisi M1 makrofaj aktivasyonu ve inflamasyonu etkiler mi?

Year 2020, , 216 - 219, 29.10.2020
https://doi.org/10.30565/medalanya.706592

Abstract

Amaç: Demir eksikliği anemisi (DEA) farklı sistemler için sorun olabilen yaygın bir bozukluktur. İnflamasyonun oluşturduğu anemi çalışılmakla birlikte, DEA’nın yol açtığı makrofaj aktivasyonu hakkında bilgi eksikliği bulunmaktadır. Bu çalışmada DEA ile makrofaj aktivasyonu arasındaki ilişkinin araştırılması amaçlanmıştır.

Hastalar ve Yöntem: Çalışmaya 88 kadın katılımcı alındı. Katılımcılar; 48 DEA hastası ve 40 sağlıklı kontroller olmak üzere iki gruba ayrıldı. M1 makrofaj aktivasyonu, triggering receptor expressed on myeloid cells-1 (TREM-1) düzeyleri ölçülerek değerlendirildi. CRP ve TREM-1 düzeyleri iki grupta karşılaştırıldı. TREM-1 düzeyleri ile vücudun demir durumu ve hemogram parametreleri arasındaki ilişki araştırıldı.

Bulgular: TREM-1 düzeyi, hasta grubunda kontrol grubuna göre daha yüksek saptandı [124.5 (6.8-770.5) pg/ml vs 48.5 (0.66-401.1) pg/ml, p=0.02]. CRP düzeyi her iki grupta benzerdi. Hasta grubunda TREM düzeyi ile hemoglobin, ortalama eritrosit hacmi, ferritin, transferrin saturasyonu, serum demiri arasında korelasyon saptanmadı (sırasıyla p değerleri 0.96, 0.14, 0.21, 0.16, 0.26).

Sonuç: Bu çalışmada DEA’da TREM-1 düzeylerinin artışının gösterilmesi, makrofaj aktivasyonunun göstergesi olabilir. DEA hastaları proinflamatuvar durumlar açısından göz önünde bulundurulabilir. Bahsedilen ilişki için daha kapsamlı çalışmalara ihtiyaç bulunmaktadır.

Supporting Institution

Yoktur.

References

  • 1. Camaschella C. Iron-Deficiency Anemia. Longo DL, editor. N Engl J Med. 2015;372(19):1832–43. PMID:25946282
  • 2. Jankowska EA, Rozentryt P, Witkowska A, Nowak J, Hartmann O, Ponikowska B, et al. Iron Deficiency Predicts Impaired Exercise Capacity in Patients With Systolic Chronic Heart Failure. J Card Fail. 2011;17(11):899–906. PMID:22041326
  • 3. Zhu L, Zhao Q, Yang T, Ding W, Zhao Y. Cellular metabolism and macrophage functional polarization. Int Rev Immunol. 2015;34(1):82–100. PMID: 25340307
  • 4. Arts RJW, Joosten LAB, van der Meer JWM, Netea MG. TREM-1: intracellular signaling pathways and interaction with pattern recognition receptors. J Leukoc Biol. Wiley-Blackwell; 2013;93(2):209–15. PMID: 23108097
  • 5. Gao S, Yi Y, Xia G, Yu C, Ye C, Tu F, et al. The characteristics and pivotal roles of triggering receptor expressed on myeloid cells-1 in autoimmune diseases. Autoimmun Rev; 2019;18(1):25–35. PMID: 30408584
  • 6. Cao C, Gu J, Zhang J. Soluble triggering receptor expressed on myeloid cell-1 (sTREM-1): a potential biomarker for the diagnosis of infectious diseases. Front Med. 2017;11(2):169–77. PMID: 28425045
  • 7. Du C, Peng L, Kou G, Wang P, Lu L, Li Y. Assessment of Serum sTREM-1 as a Marker of Subclinical Inflammation in Diarrhea-Predominant Patients with Irritable Bowel Syndrome. Dig Dis Sci. 2018;63(5):1182–91. PMID:29516326
  • 8. Biancheri P, Watson AJM. High Mucosal Plasma Cell Numbers and Low Serum TREM-1 Levels May Predict Nonresponsiveness to Anti-Tumor Necrosis Factor Therapy in Inflammatory Bowel Disease. Gastroenterology. 2019;156(1):279–81. PMID: 30472227
  • 9. Kim J, Gozal D, Bhattacharjee R, Kheirandish-Gozal L. TREM-1 and Pentraxin-3 Plasma Levels and Their Association with Obstructive Sleep Apnea, Obesity, and Endothelial Function in Children. Sleep. 2013;36(6):923–31. PMID:23729936
  • 10. Wang F, Li C, Ding FH, Shen Y, Gao J, Liu ZH, et al. Increased serum TREM-1 level is associated with in-stent restenosis, and activation of TREM-1 promotes inflammation, proliferation and migration in vascular smooth muscle cells. Atherosclerosis. 2017;267:10–8. PMID: 29080545
  • 11. Agoro R, Taleb M, Quesniaux VFJ, Mura C. Cell iron status influences macrophage polarization. PLoS One. 2018;13(5):1–20. PMID: 29771935
  • 12. Leyshon BJ, Ji P, Caputo MP, Matt SM, Johnson RW. Dietary iron deficiency impaired peripheral immunity but did not alter brain microglia in PRRSV-infected neonatal piglets. Front. Immunol. 2019;10(FEB):1–12. PMID: 30778359
  • 13. Azcárate IG, Sánchez-Jaut S, Marín-García P, Linares M, Pérez-Benavente S, García-Sánchez M, et al. Iron supplementation in mouse expands cellular innate defences in spleen and defers lethal malaria infection. Biochim Biophys Acta - Mol Basis Dis. 2017;1863(12):3049–59. PMID: 28965885
  • 14. Recalcati S, Minotti G, Cairo G. Iron regulatory proteins: from molecular mechanisms to drug development. Antioxid Redox Signal. 2010;13(10):1593–616. PMID:20214491
  • 15. Recalcati S, Locati M, Gammella E, Invernizzi P, Cairo G. Iron levels in polarized macrophages: regulation of immunity and autoimmunity. Autoimmun Rev. 2012;11(12):883–9. PMID:22449938
  • 16. Wang L, Harrington L, Trebicka E, Shi HN, Kagan JC, Hong CC, et al. Selective modulation of TLR4-activated inflammatory responses by altered iron homeostasis in mice. J Clin Invest. 2009;119(11):3322–8. PMID:19809161
  • 17. Johnson EE, Sandgren A, Cherayil BJ, Murray M, Wessling-Resnick M. Role of ferroportin in macrophage-mediated immunity. Infect Immun. 2010;78(12):5099–106. PMID: 20837712
  • 18. Flierl MA, Rittirsch D, Nadeau BA, Chen AJ, Sarma JV, Zetoune FS, et al. Phagocyte-derived catecholamines enhance acute inflammatory injury. Nature. 2007;449(7163):721–5. PMID:17914358
  • 19. Zhang Z, Zhang F, An P, Guo X, Shen Y, Tao Y, et al. Ferroportin1 deficiency in mouse macrophages impairs iron homeostasis and inflammatory responses. Blood. 2011;118(7):1912–22. PMID:21705499
  • 20. Sindrilaru A, Peters T, Wieschalka S, Baican C, Baican A, Peter H, et al. An unrestrained pro-inflammatory M1 macrophage population induced by iron impairs wound healing in humans and mice. J Clin Invest. 2011;121(3):985–97. PMID:21317534
  • 21. Askar S, Deveboynu SN, Hilal ER, Askar TK, Hismiogullari AA. Changes in pro-inflammatory cytokines and antimicrobial proteins in elderly women with iron deficiency anemia. Pakistan J Med Sci. 2019;35(2):298–301. PMID: 31086504

Does iron-deficiency anemia affect M1 macrophage activation and inflammation?

Year 2020, , 216 - 219, 29.10.2020
https://doi.org/10.30565/medalanya.706592

Abstract

Aim: Iron deficiency anemia (IDA) is a prevalent disorder and may be a problem for various systems. Anemia of inflammation has been extensively investigated before, but there is still a lack of knowledge about macrophage activation in IDA. Hence, the aim of this study was to investigate the relationship between IDA and macrophage activation.

Patients and Methods: The present study included 88 female subjects. The participants were divided into two groups: 48 IDA patients in the patient group and 40 healthy subjects in the control group. M1 macrophage activation was measured with the triggering receptor expressed on myeloid cells-1 (TREM-1). TREM-1 levels and C-reactive protein were compared between patient and control groups. The relationship between TREM-1 levels and hemogram parameters and iron status was investigated.

Results: TREM-1 levels of the patient group were significantly higher than of the control group [124.5 (6.8-770.5) pg/ml vs 48.5 (0.66-401.1) pg/ml, p=0.02], while CRP levels remained similar between the groups. There was no correlation between TREM-1 levels and hemoglobin, mean erythrocyte volume, ferritin, transferrin saturation and serum iron (p =0.96, 0.14, 0.21, 0.16, and 0.26, respectively) in IDA patients.


Conclusion:
The present study showed that IDA might increase TREM-1 levels and this condition might be a clue of macrophage activation. IDA patients should be considered in terms of pro-inflammatory conditions and further investigations are needed to clarify the association mentioned above.

References

  • 1. Camaschella C. Iron-Deficiency Anemia. Longo DL, editor. N Engl J Med. 2015;372(19):1832–43. PMID:25946282
  • 2. Jankowska EA, Rozentryt P, Witkowska A, Nowak J, Hartmann O, Ponikowska B, et al. Iron Deficiency Predicts Impaired Exercise Capacity in Patients With Systolic Chronic Heart Failure. J Card Fail. 2011;17(11):899–906. PMID:22041326
  • 3. Zhu L, Zhao Q, Yang T, Ding W, Zhao Y. Cellular metabolism and macrophage functional polarization. Int Rev Immunol. 2015;34(1):82–100. PMID: 25340307
  • 4. Arts RJW, Joosten LAB, van der Meer JWM, Netea MG. TREM-1: intracellular signaling pathways and interaction with pattern recognition receptors. J Leukoc Biol. Wiley-Blackwell; 2013;93(2):209–15. PMID: 23108097
  • 5. Gao S, Yi Y, Xia G, Yu C, Ye C, Tu F, et al. The characteristics and pivotal roles of triggering receptor expressed on myeloid cells-1 in autoimmune diseases. Autoimmun Rev; 2019;18(1):25–35. PMID: 30408584
  • 6. Cao C, Gu J, Zhang J. Soluble triggering receptor expressed on myeloid cell-1 (sTREM-1): a potential biomarker for the diagnosis of infectious diseases. Front Med. 2017;11(2):169–77. PMID: 28425045
  • 7. Du C, Peng L, Kou G, Wang P, Lu L, Li Y. Assessment of Serum sTREM-1 as a Marker of Subclinical Inflammation in Diarrhea-Predominant Patients with Irritable Bowel Syndrome. Dig Dis Sci. 2018;63(5):1182–91. PMID:29516326
  • 8. Biancheri P, Watson AJM. High Mucosal Plasma Cell Numbers and Low Serum TREM-1 Levels May Predict Nonresponsiveness to Anti-Tumor Necrosis Factor Therapy in Inflammatory Bowel Disease. Gastroenterology. 2019;156(1):279–81. PMID: 30472227
  • 9. Kim J, Gozal D, Bhattacharjee R, Kheirandish-Gozal L. TREM-1 and Pentraxin-3 Plasma Levels and Their Association with Obstructive Sleep Apnea, Obesity, and Endothelial Function in Children. Sleep. 2013;36(6):923–31. PMID:23729936
  • 10. Wang F, Li C, Ding FH, Shen Y, Gao J, Liu ZH, et al. Increased serum TREM-1 level is associated with in-stent restenosis, and activation of TREM-1 promotes inflammation, proliferation and migration in vascular smooth muscle cells. Atherosclerosis. 2017;267:10–8. PMID: 29080545
  • 11. Agoro R, Taleb M, Quesniaux VFJ, Mura C. Cell iron status influences macrophage polarization. PLoS One. 2018;13(5):1–20. PMID: 29771935
  • 12. Leyshon BJ, Ji P, Caputo MP, Matt SM, Johnson RW. Dietary iron deficiency impaired peripheral immunity but did not alter brain microglia in PRRSV-infected neonatal piglets. Front. Immunol. 2019;10(FEB):1–12. PMID: 30778359
  • 13. Azcárate IG, Sánchez-Jaut S, Marín-García P, Linares M, Pérez-Benavente S, García-Sánchez M, et al. Iron supplementation in mouse expands cellular innate defences in spleen and defers lethal malaria infection. Biochim Biophys Acta - Mol Basis Dis. 2017;1863(12):3049–59. PMID: 28965885
  • 14. Recalcati S, Minotti G, Cairo G. Iron regulatory proteins: from molecular mechanisms to drug development. Antioxid Redox Signal. 2010;13(10):1593–616. PMID:20214491
  • 15. Recalcati S, Locati M, Gammella E, Invernizzi P, Cairo G. Iron levels in polarized macrophages: regulation of immunity and autoimmunity. Autoimmun Rev. 2012;11(12):883–9. PMID:22449938
  • 16. Wang L, Harrington L, Trebicka E, Shi HN, Kagan JC, Hong CC, et al. Selective modulation of TLR4-activated inflammatory responses by altered iron homeostasis in mice. J Clin Invest. 2009;119(11):3322–8. PMID:19809161
  • 17. Johnson EE, Sandgren A, Cherayil BJ, Murray M, Wessling-Resnick M. Role of ferroportin in macrophage-mediated immunity. Infect Immun. 2010;78(12):5099–106. PMID: 20837712
  • 18. Flierl MA, Rittirsch D, Nadeau BA, Chen AJ, Sarma JV, Zetoune FS, et al. Phagocyte-derived catecholamines enhance acute inflammatory injury. Nature. 2007;449(7163):721–5. PMID:17914358
  • 19. Zhang Z, Zhang F, An P, Guo X, Shen Y, Tao Y, et al. Ferroportin1 deficiency in mouse macrophages impairs iron homeostasis and inflammatory responses. Blood. 2011;118(7):1912–22. PMID:21705499
  • 20. Sindrilaru A, Peters T, Wieschalka S, Baican C, Baican A, Peter H, et al. An unrestrained pro-inflammatory M1 macrophage population induced by iron impairs wound healing in humans and mice. J Clin Invest. 2011;121(3):985–97. PMID:21317534
  • 21. Askar S, Deveboynu SN, Hilal ER, Askar TK, Hismiogullari AA. Changes in pro-inflammatory cytokines and antimicrobial proteins in elderly women with iron deficiency anemia. Pakistan J Med Sci. 2019;35(2):298–301. PMID: 31086504
There are 21 citations in total.

Details

Primary Language English
Subjects ​Internal Diseases
Journal Section Research Article
Authors

İrfan Karahan 0000-0003-4669-1751

Aydın Çifci 0000-0001-8449-2687

Nermin Dindar Badem 0000-0002-5095-7818

Publication Date October 29, 2020
Submission Date March 19, 2020
Acceptance Date June 12, 2020
Published in Issue Year 2020

Cite

Vancouver Karahan İ, Çifci A, Dindar Badem N. Does iron-deficiency anemia affect M1 macrophage activation and inflammation?. Acta Med. Alanya. 2020;4(3):216-9.

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