title: Leukocyte fluid shear response in the presence of glucocorticoid.
abstract: Leukocytes respond to physiological fluid shear stress ( approximately 1.5 dyn/cm(2)) 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.
authors.affiliation: Department of Bioengineering, The Whitaker Institute of Biomedical Engineering, University of California, San Diego, La Jolla, CA 92093-0412, USA.
authors.forename: Shunichi
authors.initials: S
authors.lastname: Fukuda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mitsuoka
authors.forename: Geert W
authors.initials: GW
authors.lastname: Schmid-Schönbein
mesh_terms: D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D003593:Cytoplasm / Q000187:drug effects / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology*; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology; D007962:Leukocytes / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D008297:Male; D040542:Mechanotransduction, Cellular / Q000187:drug effects / Q000502:physiology*; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D011554:Pseudopodia / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000502:physiology*; D033081:Shear Strength; D013314:Stress, Mechanical
chemical_list: D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; C486332:Akap1 protein, rat; D002352:Carrier Proteins; D008565:Membrane Proteins; D003907:Dexamethasone; D000242:Cyclic AMP; D002118:Calcium