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ICAM‐1 mediated leukocyte‐endothelial cell interactions are a key to the arteriolar contribution to the inflammatory response.
Author(s) -
Sumagin Ronen,
Sarelius Ingrid H
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a773-b
Subject(s) - icam 1 , microcirculation , cremaster muscle , inflammation , vcam 1 , chemistry , cell adhesion molecule , medicine , biophysics , immunology , biology
We used inflamed arterioles in anesthetized (65 mg/kg Nembutal, ip) mouse cremaster to study the role of ICAM‐1 in leukocyte rolling. We confirm that in ICAM‐1−/− venules, leukocyte rolling velocities were significantly higher than in WT animals in controls (46.7±1.9 vs 39.8±1.3 μm/sec) and TNFα activated venules (19.4±1.0 vs11.6±0.5 μm/sec). In contrast, average leukocyte rolling velocity in ICAM‐1−/− arterioles, was significantly decreased compared to WT (32.2±1.7 vs 53.5±1.9). This is due to: lost fraction of leukocytes with rolling velocities > 65μm/sec velocity distribution profile changed from skewed (WT) to bi‐modal (−/−), indicating two populations of rolling leukocytes. We suggest that the bi‐modal velocity profile is due to a compensatory shift in the expression of other adhesion molecules following genetic intervention (knocking out the ICAM‐1 gene). When an ICAM‐1 blocking antibody was used in WT mice, the velocity profile was restored to its skewed form with consistently lower average velocity (28.3±1.1 μm/sec). Additionally, the fractional vessel length supporting leukocyte rolling was significantly reduced in both ICAM‐1−/− (68%) and blocked ICAM‐1 (55%), compared to WT mice (88%). We conclude that ICAM‐1 mediates fast leukocyte rolling in arterioles, and by increasing the probability of leukocyte‐EC interactions, enhances signaling needed for the inflammatory response.