FcÎ³ receptor III expression and morphological maturity on neutrophil are associated with higher iron level of major beta-thalassemia

Mohammad Ghozali; Tiwi Harjanti Cakranita; Adi Imam Tjahjadi; Lelani Reniarti; Reni Ghrahani; MRAA Syamsunarno; Budi Setiabudiawan; Ramdan Panigoro

doi:10.14715/cmb/2018.64.5.16

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Vol. 64 No. 5: Issue 5

Issue Published : May 1, 2018

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FcÎ³ receptor III expression and morphological maturity on neutrophil are associated with higher iron level of major beta-thalassemia

https://doi.org/10.14715/cmb/2018.64.5.16

Mohammad Ghozali

Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Indonesia

Tiwi Harjanti Cakranita

Faculty of Medicine, Universitas Padjadjaran, Indonesia

Adi Imam Tjahjadi

Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Indonesia

Lelani Reniarti

Department of Pediatrics, Faculty of Medicine, Universitas Padjadjaran, Indonesia

Reni Ghrahani

Department of Pediatrics, Faculty of Medicine, Universitas Padjadjaran, Indonesia

MRAA Syamsunarno

Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Indonesia

Budi Setiabudiawan

Department of Pediatrics, Faculty of Medicine, Universitas Padjadjaran, Indonesia

Ramdan Panigoro

Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Indonesia

Corresponding Author(s) : Mohammad Ghozali

moh.ghozali@unpad.ac.id

Cellular and Molecular Biology, Vol. 64 No. 5: Issue 5
Article Published : April 30, 2018

Abstract

Lifetime blood transfusion experienced by major Î²-thalassemia patients complicated with iron overload, therefore, may lead to their tissue injury. Ultimately, free toxic iron may alter immune response via dysregulation of immune cell activity producing prolonged effector reaction. Neutrophil as one of the vital innate immune cell despite serves as the first line of defense resulting acute inflammation has a pivotal role in chronic inflammation while releasing the toxic substance that interferes biological processes. This process is initiated by one of them by activation of FcÎ³ Receptor III (CD16), a neutrophil membrane-bound protein. A cross-sectional laboratory study involving lysed-erythrocyte heparinized whole blood of fifty pediatric major Î²-thalassemia patients treated with monoclonal antibodies i.e. CD16, CD14, and HLA-DR, dissected into CD16+ and CD16++ population using flow cytometry. Expression of FcÎ³ Receptor III was measured as Median Fluorescent Intensity (MFI). Hematology and iron status were measured. A correlation analysis was done. MFI of CD16 neutrophil [509.5 (371 – 796.5)] and ferritin level [(3209 µg/L, 1862 – 4564)] was positively correlated (r = 0.4, P = 0.007). Respectively, ferritin and serum iron were found negatively correlated with segmented neutrophils (r = -0.3, P = 0.02; r = -0.3, P = 0.02). Change in CD16 expression may implicate preliminarily neutrophil activation as a response of iron-overloaded tissue and result in chronic inflammation in Î²-thalassemia patients. However, the maturity of this cell may be altered. Future study in the understanding of neutrophil-mediated inflammation, particularly related to immune complexes and functionality, is imperative to be explored.

Keywords

Neutrophil FcÎ³ Receptor III Iron Thalassemia.

Ghozali, M., Cakranita, T. H., Tjahjadi, A. I., Reniarti, L., Ghrahani, R., Syamsunarno, M., Setiabudiawan, B., & Panigoro, R. (2018). FcÎ³ receptor III expression and morphological maturity on neutrophil are associated with higher iron level of major beta-thalassemia. Cellular and Molecular Biology, 64(5), 97–101. https://doi.org/10.14715/cmb/2018.64.5.16

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References

Kolaczkowska E, Kubes P. Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol. 2013;13(3):159-75.
Walter PB, Porter J, Evans P, Kwiatkowski JL, Neufeld EJ, Coates T, et al. Increased leucocyte apoptosis in transfused beta-thalassaemia patients. Br J Haematol. 2013;160(3):399-403.
Porter JB, Garbowski M. The pathophysiology of transfusional iron overload. Hematology/oncology clinics of North America. 2014;28(4):683-701.
Uhl B, Vadlau Y, Zuchtriegel G, Nekolla K, Sharaf K, Gaertner F, et al. Aged neutrophils contribute to the first line of defense in the acute inflammatory response. Blood,. 2017;128(19):2327-38.
Ekpenyong AE, Toepfner N, Chilvers ER, Guck J. Mechanotransduction in neutrophil activation and deactivation. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 2015;1853:3105-16.
Deicher R, Ziai F, Cohen G, Mullner M, Horl WH. High-dose parenteral iron sucrose depresses neutrophil intracellular killing capacity. Kidney Int. 2003;64(2):728-36.
Ganz T, Nemeth E. Iron homeostasis in host defence and inflammation. Nature Reviews Immunology. 2015;15(8):500-10.
Siwaponanan P, Siegers JY, Ghazali R, Ng T, McColl B, Ng GZ, et al. Reduced PU.1 expression underlies aberrant neutrophil maturation and function in beta-thalassemia mice and patients. Blood. 2017;129(23):3087-99.
Lakschevitz FS, Hassanpour S, Rubin A, Fine N, Sun C, Glogauer M. Identification of neutrophil surface marker changes in health and inflammation using high-throughput screening flow cytometry. Exp Cell Res. 2016;342(2):200-9.
Fossati G, Moots RJ, Bucknall RC, Edwards SW. Differential role of neutrophil Fcgamma receptor IIIB (CD16) in phagocytosis, bacterial killing, and responses to immune complexes. Arthritis Rheum. 2002;46(5):1351-61.
Salmon JE, Edberg JC, Kimberly RP. Fc gamma receptor III on human neutrophils. Allelic variants have functionally distinct capacities. J Clin Invest. 1990;85(4):1287-95.
Pillay J, Tak T, Kamp VM, Koenderman L. Immune suppression by neutrophils and granulocytic myeloid-derived suppressor cells: Similarities and differences. Cellular and Molecular Life Sciences. 2013;70:3813-27.
Drifte G, Dunn-Siegrist I, Tissieres P, Pugin J. Innate immune functions of immature neutrophils in patients with sepsis and severe systemic inflammatory response syndrome. Crit Care Med. 2013;41(3):820-32.
Kumar V, Sharma A. Neutrophils: Cinderella of innate immune system. Int Immunopharmacol. 2010;10(11):1325-34.
Cantinieaux B, Janssens A, Boelaert JR, Lejeune M, Vermylen C, Kerrels V, et al. Ferritin-associated iron induces neutrophil dysfunction in hemosiderosis. Journal of Laboratory and Clinical Medicine. 1999;133(4):353-61.
Ricerca BM, Di Girolamo A, Rund D. Infections in Thalassemia and Hemoglobinopathies: Focus on Therapy Related Complications. Mediterranean Journal of Hematology and Infectious Diseases. 2009;1(1):1-6.
Peake J WG, Hordern M, Suzuki K, Yamaya K, Nosaka K, Mackinnon L, Coombes JS. Changes in Neutrophil Surface Receptor Expression, Degranulation, and Respiratory Burst Activity Following Moderate and High Intensity Exercise. American Journal Of Physiology. 2004;0711:804-28.

References

Kolaczkowska E, Kubes P. Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol. 2013;13(3):159-75.

Walter PB, Porter J, Evans P, Kwiatkowski JL, Neufeld EJ, Coates T, et al. Increased leucocyte apoptosis in transfused beta-thalassaemia patients. Br J Haematol. 2013;160(3):399-403.

Porter JB, Garbowski M. The pathophysiology of transfusional iron overload. Hematology/oncology clinics of North America. 2014;28(4):683-701.

Uhl B, Vadlau Y, Zuchtriegel G, Nekolla K, Sharaf K, Gaertner F, et al. Aged neutrophils contribute to the first line of defense in the acute inflammatory response. Blood,. 2017;128(19):2327-38.

Ekpenyong AE, Toepfner N, Chilvers ER, Guck J. Mechanotransduction in neutrophil activation and deactivation. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 2015;1853:3105-16.

Deicher R, Ziai F, Cohen G, Mullner M, Horl WH. High-dose parenteral iron sucrose depresses neutrophil intracellular killing capacity. Kidney Int. 2003;64(2):728-36.

Ganz T, Nemeth E. Iron homeostasis in host defence and inflammation. Nature Reviews Immunology. 2015;15(8):500-10.

Siwaponanan P, Siegers JY, Ghazali R, Ng T, McColl B, Ng GZ, et al. Reduced PU.1 expression underlies aberrant neutrophil maturation and function in beta-thalassemia mice and patients. Blood. 2017;129(23):3087-99.

Lakschevitz FS, Hassanpour S, Rubin A, Fine N, Sun C, Glogauer M. Identification of neutrophil surface marker changes in health and inflammation using high-throughput screening flow cytometry. Exp Cell Res. 2016;342(2):200-9.

Fossati G, Moots RJ, Bucknall RC, Edwards SW. Differential role of neutrophil Fcgamma receptor IIIB (CD16) in phagocytosis, bacterial killing, and responses to immune complexes. Arthritis Rheum. 2002;46(5):1351-61.

Salmon JE, Edberg JC, Kimberly RP. Fc gamma receptor III on human neutrophils. Allelic variants have functionally distinct capacities. J Clin Invest. 1990;85(4):1287-95.

Pillay J, Tak T, Kamp VM, Koenderman L. Immune suppression by neutrophils and granulocytic myeloid-derived suppressor cells: Similarities and differences. Cellular and Molecular Life Sciences. 2013;70:3813-27.

Drifte G, Dunn-Siegrist I, Tissieres P, Pugin J. Innate immune functions of immature neutrophils in patients with sepsis and severe systemic inflammatory response syndrome. Crit Care Med. 2013;41(3):820-32.

Kumar V, Sharma A. Neutrophils: Cinderella of innate immune system. Int Immunopharmacol. 2010;10(11):1325-34.

Cantinieaux B, Janssens A, Boelaert JR, Lejeune M, Vermylen C, Kerrels V, et al. Ferritin-associated iron induces neutrophil dysfunction in hemosiderosis. Journal of Laboratory and Clinical Medicine. 1999;133(4):353-61.

Ricerca BM, Di Girolamo A, Rund D. Infections in Thalassemia and Hemoglobinopathies: Focus on Therapy Related Complications. Mediterranean Journal of Hematology and Infectious Diseases. 2009;1(1):1-6.

Peake J WG, Hordern M, Suzuki K, Yamaya K, Nosaka K, Mackinnon L, Coombes JS. Changes in Neutrophil Surface Receptor Expression, Degranulation, and Respiratory Burst Activity Following Moderate and High Intensity Exercise. American Journal Of Physiology. 2004;0711:804-28.