Exposure to fluid shear stress modulates the ability of endothelial cells to recruit neutrophils in response to tumor necrosis factor-α: a basis for local variations in vascular sensitivity to inflammation

Sajila Sheikh, G. Ed Rainger, Zoe Gale, Mahbub Rahman, Gerard B Nash

Research output: Contribution to journalArticlepeer-review

Abstract

Vascular endothelial cells are able to sense changes in the forces acting on them and respond, for instance, by modifying expression of a range of genes. However, there is little information on how such responses are integrated to modify homeostatic functions. We hypothesized that different shear stresses experienced in different regions of the circulation might influence endothelial sensitivity to inflammatory stimuli. We cultured human endothelial cells in tubes and exposed them for varying periods to shear stresses ranging from those typically found in postcapillary venules to those in arteries. When tumor necrosis factor-α was included in the flow cultures, we found startling differential effects of shear stress on the ability of endothelial cells to induce adhesion and migration of flowing neutrophils. Compared with static cultures, endothelial cells cultured at low shear stress (0.3 Pa) captured similar numbers of neutrophils but failed to induce their transendothelial migration. After exposure of endothelial cells to high shear stress (1.0 or 2.0 Pa), capture of neutrophils was largely ablated. The modification in response was detectable after 4 hours of exposure to flow but was much greater after 24 hours. From analysis of gene expression, loss of capture or migration was attributable to reduction in tumor necrosis factor–induced expression of selectins or CXC-chemokines, respectively. Thus, conditioning of endothelial cells by different flow environments may underlie variations in susceptibility to inflammation between different tissues or parts of the vascular tree.
Original languageEnglish
Pages (from-to)2828–2834
Number of pages7
JournalBlood
Volume102
Issue number8
DOIs
Publication statusPublished - 15 Oct 2003

Keywords

  • Cell Adhesion and Motility
  • Chemokines, Cytokines, and Interleukins
  • gene expression
  • Hemostasis
  • thrombosis
  • vascular biology
  • phagocyte
  • signal transduction

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