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


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 microm 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 microm(2) 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.
Sumagin
Ronen
R
Department of Pharmacology and Physiology, University of Rochester, New York, USA.
Lamkin-Kennard
Kathleen A
KA
Sarelius
Ingrid H
IH
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D042783:Endothelial Cells / Q000502:physiology; D018056:Hemorheology; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D018482:Muscle, Skeletal / Q000098:blood supply; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014699:Venules / Q000033:anatomy & histology* / Q000502:physiology*
C090509:Icam1 protein, mouse; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1