Objective To evaluate the efficacy and reversible effect of anti-VCAM-1 ultrasound-targeted microbubbles on extracorporeal circulation (ECC) related bone marrow neutrophil releasing.
Methods Thirty-six male SD rats were randomly divided into 6 groups with 6 rats in each group, including an antibody group (group A), antibody with ultrasound group (group AU), targeted microbubble group (group T), targeted microbubble rupture group (group TU), post-ECC plasma simulation group (group MC) and control group (group C) after in situ perfusion model establishment. Rats in group C received buffer perfusion for 4 cycles, and rats in other groups received perfusion for 5 cycles. After buffer perfusion for the first cycle, post-ECC plasma was infused to each group from the second cycle to the fifth cycle in group MC, A, AU, T and TU. Rats in group A and AU received injection with anti-VCAM-1 antibodies, while rats in group T and TU were given anti-VCAM-1 targeted microbubbles after the second perfusion cycle. Same ultrasound radiation was given to group AU and TU in the third perfusion cycle. Neutrophil counts from perfusate were compared among the 6 groups.
Results Under simulated inflammatory condition after ECC, compared with group MC, significant reduction of neutrophil count released from bone marrow was found in group A and T, especially in group T (P < 0.05). After ultrasonic radiation, neutrophil mobilization recovered in group TU and its neutrophil count was significantly higher than that of group T (P < 0.05). There was no significant difference in neutrophil count between group A and AU in each perfusion cycle (P > 0.05).
Conclusions Anti-VCAM-1 targeted microbubbles can block the binding of VCAM-1 and its ligand, and form a barrier on the surface of bone marrow sinusoids endothelium to inhibit neutrophils migrating and releasing. The binding of VCAM-1 and its ligand on microbubbles is separated by cavitation of disrupting microbubbles with ultrasound, and neutrophils recover the ability to cross the sinusoidal endothelium of bone marrow in inflammatory conditions to achieve the controllability of neutrophil releasing.
Citation：
GANChang-ping, QIUXu, ZHANGJing-yi, ANQi, SHIYing-kang. Reversible Effect of Anti-VCAM-1 Ultrasound-targeted Microbubbles on Extracorporeal Circulation Related Bone Marrow Neutrophil Releasing. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2015, 22(2): 146-150. doi: 10.7507/1007-4848.20150041
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- 1. Summers C, Rankin SM, Condliffe AM. Neutrophil kinetics in health and disease. Trends Immunol, 2010, 31(8):318-324.
- 2. Butterfield TA, Best TM, Merrick MA. The dual roles of neutrophils and macrophages in inflammation:a critical balance between tissue damage and repair. J Athl Train, 2006, 41(4):457-465.
- 3. Smith JA. Neutrophils, host defense, and inflammation:a doubleedged sword. J Leukoc Biol, 1994, 56(6):672-686.
- 4. 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.
- 5. Grocott HP, Mackensen GB, Newman MF, et al. Neurological injury during cardiopulmonary bypass in the rat. Perfusion, 2001, 16(1):75-81.
- 6. Burns RC, Rivera-Nieves J, Moskaluk CA, et al. Antibody blockade of ICAM-1 and VCAM-1 ameliorates inflammation in the SAMP-1/Yit adoptive transfer model of Crohn's disease in mice. Gastroenterology, 2001, 121(6):1428-1436.
- 7. Kaufmann BA, Sanders JM, Davis C, et al. Molecular imaging of inflammation in atherosclerosis with targeted ultrasound detection of vascular cell adhesion molecule-1. Circulation, 2007, 116(3):276-284.
- 8. Behm CZ, Kaufmann BA, Carr C, et al. Molecular imaging of endothelial vascular cell adhesion molecule-1 expression and inflammatory cell recruitment during vasculogenesis and ischemiamediated arteriogenesis. Circulation, 2008, 117(22):2902-2911.
- 9. Chen ZY, Lin Y, Yang F, et al. Gene therapy for cardiovascular disease mediated by ultrasound and microbubbles. Cardiovasc Ultrasound, 2013, 11(1):11.
- 10. Deng CX. Targeted drug delivery across the blood-brain barrier using ultrasound technique. Ther Deliv, 2010, 1(6):819-848.
