RESEARCH PAPER
Osteopontin enhances donor-specific alloreactivity of human peripheral blood mononuclear cells
Beata Kaleta 1  
 
 
More details
Hide details
1
Department of Clinical Immunology, Medical University, Warsaw, Poland
CORRESPONDING AUTHOR
Beata Kaleta   

Department of Clinical Immunology, Medical University of Warsaw, Poland, Nowogrodzka 59 St., 02-006, Warsaw, Poland
 
J Pre Clin Clin Res. 2019;13(3):106–109
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Graft-versus-host disease (GVHD) is a serious complication after allogeneic haematopoietic stem cell transplantation (HSCT). Osteopontin (OPN) is a pleiotropic glycoprotein, which plays a significant role in the regulation of biomineralization, wound healing, and cellular immunity. Numerous studies have demonstrated that elevated OPN levels are associated with the pathogenesis of multiple autoimmune and inflammatory conditions. However, its role in GVHD and transplant immunology is poorly understood.

Objective:
The the aim of the study was to investigate the effects of OPN on human peripheral blood mononuclear cells (PBMCs) proliferation in a mixed lymphocyte reaction (MLR).

Material and methods:
PBMCs were isolated from the venous blood of 20 participants. Cell proliferation was examined at the DNA synthesis level by measurements of 3H-thymidine incorporation. Radioactivity was used to calculate the MLR stimulation index (SI). Cell viability was determined using the trypan blue exclusion method.

Results:
OPN enhanced the proliferative response of human alloactivated PBMCs in MLR. Statistically significant results were observed for OPN of 100, 200, 300 and 400 ng/mL (P=0.013, P=0.009; P=0.003 and P < 0.001, respectively). Moreover, OPN increased SI in a dose-dependent way (P=0.011, P=0.007; P=0.002 and P < 0.001, respectively). In addition, this protein did not affect cells viability.

Conclusions:
The results confirm the assumption that OPN may affect the outcome after HSCT; however, future investigation is needed to verify whether it may serve as a valuable predictive and prognostic marker of GVHD.

 
REFERENCES (23)
1.
Ferrara JL, Levine JE, Reddy P, Holler E. Graft-versus-host disease. Lancet. 2009; 373(9674): 1550–1561. https://doi.org/10.1016/S0140- 6736(09)60237-3.
 
2.
Petersdorf EW. Role of major histocompatibility complex variation in graft-versus-host disease after hematopoietic cell transplantation. F1000Res. 2017; 6: 617. https://doi.org/10.12688/f1000....
 
3.
Moreno DF, Cid J. Graft-versus-host disease. Med Clin (Barc). 2019; 152(1): 22–28. https://doi.org/10.1016/j.medc....
 
4.
Fisher LW, Torchia DA, Fohr B, Young MF, Fedarko NS. Flexible structures of SIBLING proteins, bone sialoprotein, and osteopontin. Biochem Biophys Res Commun. 2001; 280(2): 460–465. https://doi. org/10.1006/bbrc.2000.4146.
 
5.
Icer MA, Gezmen-Karadag M. The multiple functions and mechanisms of osteopontin. Clin Biochem. 2018; 59: 17–24. https://doi.org/10.1016/j. clinbiochem.2018.07.003.
 
6.
Subraman V, Thiyagarajan M, Malathi N, Rajan ST. OPN – Revisited. J Clin Diagn Res. 2015; 9(6): ZE10-ZE13. https://doi.org/10.7860/ JCDR/2015/12872.6111.
 
7.
Rittling SR, Singh R. Osteopontin in Immune-mediated Diseases. J Dent Res. 2015; 94(12): 1638–1645. https://doi.org/10.1177/002203....
 
8.
Clemente N, Raineri D, Cappellano G, Boggio E, Favero F, Soluri MF et al. Osteopontin Bridging Innate and Adaptive Immunity in Autoimmune Diseases. J Immunol Res. 2016; 7675437. https://doi. org/10.1155/2016/7675437.
 
9.
Lok ZSY, Lyle AN. Osteopontin in Vascular Disease. Arterioscler Thromb Vasc Biol. 2019; 39(4): 613–622. https://doi.org/10.1161/ ATVBAHA.118.311577.
 
10.
Uede T. Osteopontin, intrinsic tissue regulator of intractable inflammatory diseases. Pathol Int. 2011; 61(5): 265–280. https://doi. org/10.1111/j.1440-1827.2011.02649.x.
 
11.
Wen Y, Jeong S, Xia Q, Kong X. Role of Osteopontin in Liver Diseases. Int J Biol Sci. 2016; 12(9): 1121–1128. https://doi.org/10.7150/ijbs.1....
 
12.
K omine-Aizawa S, Masuda H, Mazaki T, Shiono M, Hayakawa S, Takayama T. Plasma osteopontin predicts inflammatory bowel disease activities. Int Surg. 2015; 100(1): 38–43. https://doi.org/10.9738/ INTSURG-D-13-00160.1.
 
13.
Konno S, Kurokawa M, Uede T, Nishimura M, Huang SK. Role of osteopontin, a multifunctional protein, in allergy and asthma. Clin Exp Allergy. 2011; 41(10): 1360–1366. https://doi.org/10.1111/j.1365... 2222.2011.03775.x.
 
14.
Zhu Q, Luo X, Zhang J, Liu Y, Luo H, Huang Q et al. Osteopontin as a Potential Therapeutic Target for Ischemic Stroke. Curr Drug Deliv. 2017; 14(6): 766–772. https://doi.org/10.2174/156720....
 
15.
Alchi B, Nishi S, Kondo D, Kaneko Y, Matsuki A, Imai N et al. Osteopontin expression in acute renal allograft rejection. Kidney Int. 2005; 67(3): 886–896. https://doi.org/10.1111/j.1523....
 
16.
Sayılan Şen H, Kılıçaslan Ayna T, Şentürk Çiftçi H, Kalayoğlu Beşışık S, Onal EA, Akçay A et al. The predictive value of stimulation index calculated by modified mixed lymphocyte culture in the detection of GVHD following hematopoietic stem cell transplantation. Turk J Haematol. 2010; 27(4): 263–268. https://doi.org/10.5152/tjh.20....
 
17.
Kawakami K, Minami N, Matsuura M, Iida T, Toyonaga T, Nagaishi K et al. Osteopontin attenuates acute gastrointestinal graft-versus-host disease by preventing apoptosis of intestinal epithelial cells. Biochem Biophys Res Commun. 2017; 485(2): 468–475. https://doi.org/10.1016/j. bbrc.2017.02.047.
 
18.
Zhao F, Zhang Y, Wang H, Jin M, He S, Shi Y et al. Blockade of osteopontin reduces alloreactive CD8+ T cell-mediated graft-versushost disease. Blood. 2011; 117(5): 1723–1733. https://doi.org/10.1182/ blood-2010-04-281659.
 
19.
Lin YH, Yang-Yen HF. The osteopontin-Cd44 survival signal involves activation of the phosphatidylinositol 3-kinase/Akt signaling pathway. J Biol Chem. 2001; 276(49): 46024–46030. https://doi.org/10.1074/jbc. M105132200.
 
20.
Yu X, Zheng Y, Zhu X, Gao X, Wang C, Sheng Y et al. Osteopontin promotes hepatocellular carcinoma progression via the PI3K/AKT/ Twist signaling pathway. Oncol Lett. 2018; 16(4): 5299–5308. https:// doi.org/10.3892/ol.2018.9281.
 
21.
Jin ZK, Tian PX, Wang XZ, Xue WJ, Ding XM, Zheng J et al. Kidney injury molecule-1 and osteopontin: new markers for prediction of early kidney transplant rejection. Mol Immunol. 2013; 54 (3–4): 457–464. https://doi.org/10.1016/j.moli....
 
22.
Rouschop KM, Roelofs JJ, Sylva M, Rowshani AT, Ten Berge IJ, Weening JJ et al. Renal expression of CD44 correlates with acute renal allograft rejection. Kidney Int. 2006; 70(6): 1127–1134. https://doi.org/10.1038/ sj.ki.5001711.
 
23.
Ouyang J, He J, Fan YS, Fan CB, Sun HY, Wen DG. [Expressions of interleukin-15 and osteopontin mRNA in early stage of acute rejection of renal allograft in rats]. Article in Chinese. Zhonghua Yi Xue Za Zhi. 2010; 90(10): 698–702.
 
eISSN:1898-7516
ISSN:1898-2395