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Published online before print January 22, 2004, 10.1148/radiol.2303020897
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(Radiology 2004;230:735-742.)
© RSNA, 2004

Experimental Studies

Interaction with Leukocytes: Phospholipid-stabilized versus Albumin-Shell Microbubbles1

Hiroto Takeuchi, MD, Koji Ohmori, MD, PhD, Isao Kondo, MD, PhD, Kaori Shinomiya, MD, PhD, Akira Oshita, MD, PhD, Yuichiro Takagi, MD, Junji Yoshida, MD, Katsufumi Mizushige, MD, PhD and Masakazu Kohno, MD, PhD

1 From the Second Department of Internal Medicine, Kagawa University School of Medicine, 1750-1, Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. Received August 1, 2002; revision requested September 23; final revision received May 27, 2003; accepted June 10. Supported by grant for Hypertensive Arteriosclerosis Research Award, Tokyo, Japan. Address correspondence to K.O. (e-mail: komori@kms.ac.jp).

PURPOSE: To confirm that BR14 microbubbles (MBs) can be phagocytosed by activated leukocytes, to determine their stability after phagocytosis, and to evaluate how such characteristics influence the fate of neutrophils containing MBs after insonation.

MATERIALS AND METHODS: BR14 and human albumin MBs (2 x 107/mL) were incubated with activated human neutrophils (2 x 106/mL) to allow phagocytosis. Deflation rate of the phagocytosed MBs after pulsed insonation (one burst per second for 5 seconds) at 1.8 MHz with peak negative pressure of -540 kPa or -1,340 kPa, lactate dehydrogenase (LDH) leakage, and terminal deoxynucleotidyl transferase–mediated dUTP nick end-labeling stain–positive cell count after insonation were compared between the two agents.

RESULTS: At -540 kPa, phagocytosed MBs remained nearly unchanged for both agents after insonation. At -1,340 kPa, although human albumin MBs were disrupted on the first or second burst, BR14 MBs remained undisrupted. After -540-kPa insonation, a similar number of apoptotic cells appeared in neutrophils containing human albumin and BR14 MBs. At -540 kPa, LDH leakage was limited in human albumin MBs and BR14 MBs. At -1,340 kPa, LDH leakage was significantly increased in human albumin MBs and BR14 MBs (P < .01, both vs -540 kPa). Apoptotic cells were significantly decreased in human albumin MBs and BR14 MBs (P < .01, both vs -540 kPa). LDH leakage was lower and apoptotic cell count was greater in BR14 MB–containing neutrophils than in human albumin MB–containing neutrophils (both P < .01).

CONCLUSION: Compared with human albumin MBs, BR14 MBs were more stable after phagocytosis with insonation. This stability is associated with less disruption and greater induction of apoptosis in leukocytes after relatively high-pressure insonation in the range for diagnostic use.

© RSNA, 2004

Index terms: Leukocytes • Microbubbles • Ultrasound (US), contrast media • Ultrasound (US), experimental studies




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