The Effect of Up-regulating CXCR4 Expression on Bone Marrow Neutrophils in Modulating its ECC-related Rapid Release_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

 GANChang-ping , QIUXu , ANQi , SHIYing-kang

Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu 610041, P. R. China;

Corresponding?author：

GANChang-ping, Email: ganchangping@hotmail.com

Keywords：

Extracorporeal circulation (ECC); Neutrophils; Bone marrow; Chemokine (C-X-C motif)receptor 4 (CXCR4)

DOI：

10.7507/1007-4848.20150019

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective Based on the rat in situ perfusion system, to explore the effect of up-regulating Chemokine (C-X-C motif) receptor 4 (CXCR4) expression on bone marrow neutrophils in modulating its ECC-related rapid release. Methods Twelve SD rats were randomly divided into fucoidan perfusion group (F, n=6) and control group (C, n=6) after in situ perfusion system establishment. Rats in F group received perfusion of fucoidan solution (total volume 6 ml, 1 h) and C group received buffer only. Femurs from two groups were dissected after one-hour perfusion and bone marrow tissues were collected. The neutrophil CXCR4 expression in two groups were compared using flowcytometry. Eighteen SD rats were randomly divided into fucoidan perfusion group (F', n=6), fucoidan and AMD-3100 perfusion group (F+AMD3100, n=6) and control group (C', n=6) after in situ perfusion system establishment. Rats received desired interventions before stimulation from ECC plasma. After that, 40-min perfusions of buffer were added and total counts of neutrophil in perfusates were compared. Results The percentages of CXCR4 (+) cell and CXCR4 expression fluorescence in F group were 4.71%±0.21% and 161.3±7.8 respectively while the values were 1.11%±0.11% and 58.4±6.5 respectively in C group. Values in F group were both significantly higher than those in C group (P<0.05). The total counts of neutrophil in perfusates from F' group, F+AMD3100 and C' group were 261 393.7±12 470.6, 872 635.2±10 430.6 and 818 675.2±10 708.8, respectively. Statistically differences were observed between each other (P<0.05). Conclusion Bone marrow neutrophil CXCR4 expression of SD rat could be effectively up-regulated by perfusion of fucoidan within the in situ perfusion system. ECC-plasma-stimulated bone marrow neutrophil release in rat could be inhibited by fucoidan induced up-regulation of neutrophil CXCR4 expression, and this inhibition effect could be canceled by AMD-3100 intervention.

Citation： GANChang-ping, QIUXu, ANQi, SHIYing-kang. The Effect of Up-regulating CXCR4 Expression on Bone Marrow Neutrophils in Modulating its ECC-related Rapid Release. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2015, 22(1): 66-70. doi: 10.7507/1007-4848.20150019 Copy

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13.	Petty JM, Sueblinvong V, Lenox CC, et al. Pulmonary stromalderived factor-1 expression and effect on neutrophil recruitment during acute lung injury. J Immunol, 2007, 178(12):8148-8157.
14.	Lau TT, Wang DA. Stromal cell-derived factor-1 (SDF-1):homing factor for engineered regenerative medicine. Expert Opin Biol Ther, 2011, 11(2):189-197.
15.	Woiakowski W, Kucia M, Liu R, et al. Circulating very small embryonic-like cells in cardiovascular disease. J Cardiovasc Transl Res, 2011, 4(2):138-144.

1. ?Clark SC. Lung injury after cardiopulmonary bypass. Perfusion, 2006, 21(4):225-228.
2. A?irba?li M, Nguyen ML, Win K, et al. Inflammatory and hemostatic response to cardiopulmonary bypass in pediatric population:feasibility of seriological testing of multiple biomarkers. Artif Organs, 2010, 34(11):987-995.
3. Hendrix CW, Collier AC, Lederman MM, et al. Safety, pharmacokinetics, and antiviral activity of AMD3100, a selective CXCR4 receptor inhibitor, in HIV-1 infection. J Acquir Immune Defic Syndr, 2004, 37(2):1253-1262.
4. Eash KJ, Greenbaum AM, Gopalan PK, et al. CXCR2 and CXCR4 antagonistically regulate neutrophil trafficking from murine bone marrow. J Clin Invest, 2010, 120(7):2423-2431.
5. Ding Z, Issekutz TB, Downey GP, et al. L-selectin stimulation enhances functional expression of surface CXCR4 in lymphocytes:implications for cellular activation during adhesion and migration. Blood, 2003, 101(11):4245-4252.
6. Grocott HP, Mackensen GB, Newman MF, et al. Neurological injury during cardiopulmonary bypass in the rat. Perfusion, 2001, 16(1):75-81.
7. Burdon PC, Martin C, Rankin SM. The CXC chemokine MIP-2 stimulates neutrophil mobilization from the rat bone marrow in a CD49d-dependent manner. Blood, 2005, 105(6):2543-2548.
8. Diaz GA, Gulino AV. WHIM syndrome:a defect in CXCR4 signaling. Curr Allergy Asthma Rep, 2005, 5(5):350-355.
9. Martin C, Burdon PCE, Bridger G, et al. Chemokines acting via CXCR2 and CXCR4 control the release of neutrophils from the bone marrow and their return following senescence. Immunity, 2003, 19(4):583-593.
10. Duchesneau P, Gallagher E, Walcheck B, et al. Up-regulation of leukocyte CXCR4 expression by sulfatide:an L-selectin-dependent pathway on CD4+ T cells. Eur J Immunol, 2007, 37(10):2949-2960.
11. 倪俊, 陳玉林, 于寶軍. 硫苷脂、燙傷血清對大鼠中性粒細胞產生超氧陰離子的影響. 第二軍醫大學學報, 1998, 19(z1):66-68.
12. 倪俊, 于寶軍, 顧海峰, 等. 硫苷脂減輕嚴重燒傷延遲復蘇大鼠遠隔臟器能量代謝紊亂. 中國微循環, 2007, 11(6):366-367.
13. Petty JM, Sueblinvong V, Lenox CC, et al. Pulmonary stromalderived factor-1 expression and effect on neutrophil recruitment during acute lung injury. J Immunol, 2007, 178(12):8148-8157.
14. Lau TT, Wang DA. Stromal cell-derived factor-1 (SDF-1):homing factor for engineered regenerative medicine. Expert Opin Biol Ther, 2011, 11(2):189-197.
15. Woiakowski W, Kucia M, Liu R, et al. Circulating very small embryonic-like cells in cardiovascular disease. J Cardiovasc Transl Res, 2011, 4(2):138-144.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

The Effect of Up-regulating CXCR4 Expression on Bone Marrow Neutrophils in Modulating its ECC-related Rapid Release

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