Leukocyte rolling in Peyer's Patch (PP) high endothelial venules (HEV) occurs at different characteristic velocites in L-selectin- and β7 integrin-deficient mice
Both L-selectin and β7 integrins have been implicated in lymphocyte homing to Peyer's Patches in vivo. In order to understand the contributions of both L-selectin and β7 integrins to leukocyte rolling in PP, we have measured the leukocyte rolling flux fraction and rolling velocity in hemodynamically similar PP HEV using in vivo epiluminescence intravital microscopy in wild-type, L-selectin-deficient (L -/-), and β7 integrin-deficient (β7 -/-) mice. Intravascular leukocytes were stained using acridine red and average blood flow velocities in PP HEV were measured using fluorescent beads. The rolling flux fractions in wild-type (98±15%) and β7 -/- (85±10%) mice were not statistically different. In both wild-type and β7 -/- mice, the rolling flux fraction was reduced by 80-90% with the blocking L-selectin mAb MEL-14 (p<0.01). Conversely, in L -/- mice, the rolling flux fraction was only 19±6% (p<0.01 vs. wild-type and β7 -/- mice). The rolling velocity distribution in wild-type mice was bimodal, with peaks around 30 and 95 μm/s. β7 -/- mice had a velocity distribution with one peak at ∼85 μm/s. Conversely, L -/- mice had a unimodal velocity distribution with the peak at ∼25 μm/s. Together, these data highlight a role for β7 integrins in mediating leukocyte rolling in PP HEV in vivo.
Kunkel, EJ; Wagner, N; Tedder, TF; Ley, K
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