A separate role for ICAM-1 and fluid shear in regulating leukocyte interactions with straight regions of venular wall and venular convergences

Ronen Sumagin, Kathleen A. Lamkin-Kennard, Ingrid H. Sarelius*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Objective: Variation in expression of adhesion molecules plays a key role in regulating leukocyte behavior, but the contribution of fluid shear to these interactions cannot be ignored. Here, we dissected the effects of each of these factors on leukocyte behavior in different venular regions. Materials and Methods: Leukocyte behavior was quantified in blood-perfused microvascular networks in anesthetized mouse cremaster muscle, using intravital confocal microscopy. ICAM-1 expression and fluid shear rate were quantified by using ICAM-1 fluorescent labeling, fluorescent particle tracking, and computational fluid dynamics. Results: Tumor necrosis factor alpha induced an increase in ICAM-1 expression and abolished the differences observed among control venules of different sizes. Consequently, leukocyte adhesion was increased to a similar level across all vessel sizes [5.1±0.46 leukocytes/100 ±m vs. 2.1±0.47 (control)], but remained significantly higher in venular convergences (7.8±0.4). Leukocyte transmigration occurred primarily in the smallest venules and venular convergences (23.9±5.1 and 31.9±2.7 leukocytes/10,000 μm2 tissue, respectively). In venular convergences, the two inlet vessels are predicted to create a region of low velocity, increasing leukocyte adhesion probability. Conclusions: In straight regions of different-sized venules, the variability in ICAM-1 expression accounts for the differences in leukocyte behavior; in converging regions, fluid shear potentially has a greater effect on leukocyte endothelial cell interactions.

Original languageEnglish (US)
Pages (from-to)508-520
Number of pages13
JournalMicrocirculation
Volume16
Issue number6
DOIs
StatePublished - 2009

Keywords

  • Convergences
  • ICAM-1
  • In vivo
  • Leukocyte adhesion
  • Leukocyte rolling
  • Mouse
  • Shear rate
  • Vessel size

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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