Mice lacking two or all three selectins demonstrate overlapping and distinct functions for each selectin

U Jung, K Ley - The Journal of Immunology, 1999 - journals.aai.org
U Jung, K Ley
The Journal of Immunology, 1999journals.aai.org
Selectins support the capture and rolling of leukocytes in venules at sites of inflammation
and in lymphocyte homing. Gene-targeted mice with null mutations at the L-, E-, or P-selectin
locus develop normally and show mild (E−/−) to moderate (P−/−, L−/−) defects in
inflammatory cell recruitment. Mice lacking both P-and E-selectin (E/P−/−) have severe
neutrophilia and spontaneous skin infections that limit their life span. Other combinations of
selectin deficiency have not been investigated. We have generated novel mice lacking L …
Abstract
Selectins support the capture and rolling of leukocytes in venules at sites of inflammation and in lymphocyte homing. Gene-targeted mice with null mutations at the L-, E-, or P-selectin locus develop normally and show mild (E−/−) to moderate (P−/−, L−/−) defects in inflammatory cell recruitment. Mice lacking both P-and E-selectin (E/P−/−) have severe neutrophilia and spontaneous skin infections that limit their life span. Other combinations of selectin deficiency have not been investigated. We have generated novel mice lacking L-and P-selectin (L/P−/−), L-and E-selectin (L/E−/−), or all three selectins (E/L/P−/−) by bone marrow transplantation. L/P−/− mice (only E-selectin present) show an absence of leukocyte rolling after trauma and severely reduced rolling (by∼ 90%) in inflammation induced by TNF-α. Residual rolling in L/P−/− mice was very slow (3.6±0.2 μm/s after TNF-α). L/E−/− mice (only P-selectin present) showed rolling similar to that of L−/− at increased velocities (15.1±0.3 μm/s). The number of adherent leukocytes after 2 or 6 h of TNF-α treatment was not significantly reduced in L/E−/− or L/P−/− mice. E/L/P−/− mice showed very little rolling after TNF-α, all of which was blocked by mAb to α 4 integrin. Adherent and emigrated neutrophils were significantly reduced at 6 h after TNF-α. We conclude that any one of the selectins can support some neutrophil recruitment but eliminating all three selectins significantly impairs neutrophil recruitment.
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