TY - JOUR
T1 - Control of leukocyte rolling velocity in TNF-α-induced inflammation by LFA-1 and Mac-1
AU - Dunne, Jessica L.
AU - Ballantyne, Christie M.
AU - Beaudet, Arthur L.
AU - Ley, Klaus
PY - 2002/1/1
Y1 - 2002/1/1
N2 - Previously it was shown that β2-integrins are necessary for slow leukocyte rolling in inflamed venules. In this study, mice that are deficient for either one of the β2-integrins, αLβ2 (LFA-1) or αMβ2 (Mac-1), were used to determine which of the β2-integrins are responsible for slowing rolling leukocytes. The cremaster muscles of these mice were treated with tumor necrosis factor-α and prepared for intravital microscopy. The average rolling velocities in venules were elevated in LFA-1-/- mice (11.0 ± 0.7 μm/s) and Mac-1-/- mice (10.1 ± 1.1 μm/s) compared to wild-type mice (4.8 ± 0.3 μm/s; P < .05), but were lower than in CD18-/- mice (28.5 ± 2.1 μm/s). When both LFA-1 and Mac-1 were absent or blocked, rolling velocity became dependent on shear rate and approached that of CD18-/- mice. In addition, leukocyte adhesion efficiency was decreased in LFA-1-/- mice to near CD18-/- levels, but decreased only slightly in Mac-1-/- mice. Thus, both LFA-1 and Mac-1 contribute to slowing down rolling leukocytes, although LFA-1 is more important than Mac-1 in efficiently inducing firm adhesion.
AB - Previously it was shown that β2-integrins are necessary for slow leukocyte rolling in inflamed venules. In this study, mice that are deficient for either one of the β2-integrins, αLβ2 (LFA-1) or αMβ2 (Mac-1), were used to determine which of the β2-integrins are responsible for slowing rolling leukocytes. The cremaster muscles of these mice were treated with tumor necrosis factor-α and prepared for intravital microscopy. The average rolling velocities in venules were elevated in LFA-1-/- mice (11.0 ± 0.7 μm/s) and Mac-1-/- mice (10.1 ± 1.1 μm/s) compared to wild-type mice (4.8 ± 0.3 μm/s; P < .05), but were lower than in CD18-/- mice (28.5 ± 2.1 μm/s). When both LFA-1 and Mac-1 were absent or blocked, rolling velocity became dependent on shear rate and approached that of CD18-/- mice. In addition, leukocyte adhesion efficiency was decreased in LFA-1-/- mice to near CD18-/- levels, but decreased only slightly in Mac-1-/- mice. Thus, both LFA-1 and Mac-1 contribute to slowing down rolling leukocytes, although LFA-1 is more important than Mac-1 in efficiently inducing firm adhesion.
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U2 - 10.1182/blood.V99.1.336
DO - 10.1182/blood.V99.1.336
M3 - Article
C2 - 11756189
AN - SCOPUS:0036090346
SN - 0006-4971
VL - 99
SP - 336
EP - 341
JO - Blood
JF - Blood
IS - 1
ER -