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Originally published online as doi:10.1189/jlb.1003464 on January 14, 2004

Published online before print January 14, 2004
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(Journal of Leukocyte Biology. 2004;75:664-670.)
© 2004 by Society for Leukocyte Biology

Leukocyte fluid shear response in the presence of glucocorticoid

Shunichi Fukuda*, Hiroshi Mitsuoka{dagger} and Geert W. Schmid-Schönbein*,1

* Department of Bioengineering and The Whitaker Institute of Biomedical Engineering, University of California San Diego, La Jolla, California; and
{dagger} Second Department of Surgery, Hamamatsu University School of Medicine, Japan

1Correspondence: Department of Bioengineering, The Whitaker Institute of Biomedical Engineering, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0412. E-mail: gwss{at}bioeng.ucsd.edu

Leukocytes respond to physiological fluid shear stress (~1.5 dyn/cm2) by cytoplasmic reorganization. The cytoplasm is also influenced, however, by glucocorticoids. In this study, we explore how glucocorticoids may affect the leukocyte fluid shear response. Normal leukocytes, exposed to fluid shear in vitro during active migration, retract pseudopods accompanied by modestly decreasing intracellular calcium ions. In contrast, dexamethasone (DX)-treated leukocytes project pseudopods after shear exposure with a significant rise in intracellular calcium ions, an effect that can be blocked by voltage-dependent calcium channel blockers. Although a cyclic adenine monophosphate analog blocks calcium influx and pseudopod projection by DX, inhibition of A-kinase induces reversal of the shear response, as seen with DX treatment. DX also reverses the leukocyte shear response in vivo in the rat circulation. Leukocytes that adhere to the endothelium in postcapillary venules of control rats return into the circulation only after pseudopod retraction, and in DX-treated rats, adherent leukocytes return into the circulation still with projecting pseudopods. The fraction of circulating leukocytes with pseudopods in DX-treated rats is higher than in controls. Thus, the reversal of leukocyte shear response by glucocorticoids may contribute to an enhanced incidence of circulating leukocytes with pseudopods, a process that affects the kinetics of these cells in the microcirculation.

Key Words: mechanotransduction • fluid shear stress • pseudopod formation




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[Abstract] [Full Text] [PDF]


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