Leukocyte fluid shear response in the presence of glucocorticoid

Journal of Leukocyte Biology

Shunichi Fukuda¹  Hiroshi Mitsuoka²  Geert W. Schmid-Schönbein¹ 

[1] Department of Bioengineering and The Whitaker Institute of Biomedical Engineering, University of California San Diego, La Jolla, California; and Department of Bioengineering and The Whitaker Institute of Biomedical Engineering, University of California San Diego, La Jolla, California; and Department of Bioengineering and The Whitaker Institute of Biomedical Engineering, University of California San Diego, La Jolla, California; and;Second Department of Surgery, Hamamatsu University School of Medicine, Japan Second Department of Surgery, Hamamatsu University School of Medicine, Japan Second Department of Surgery, Hamamatsu University School of Medicine, Japan

关键词: mechanotransduction;    fluid shear stress;    pseudopod formation;   

DOI  :  10.1189/jlb.1003464

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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.

【 授权许可】

Unknown