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

First Author  Jung U Year  1999
Journal  J Immunol Volume  162
Issue  11 Pages  6755-62
PubMed ID  10352295 Mgi Jnum  J:55032
Mgi Id  MGI:1337157 Doi  10.4049/jimmunol.162.11.6755
Citation  Jung U, et al. (1999) Mice lacking two or all three selectins demonstrate overlapping and distinct functions for each selectin. J Immunol 162(11):6755-62
abstractText  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 approximately 90%) in inflammation induced by TNF-alpha. Residual rolling in L/P-/- mice was very slow (3.6 +/- 0.2 micrometers/s after TNF-alpha). L/E-/- mice (only P-selectin present) showed rolling similar to that of L-/- at increased velocities (15.1 +/- 0.3 micrometer/s). The number of adherent leukocytes after 2 or 6 h of TNF-alpha treatment was not significantly reduced in L/E-/- or L/P-/- mice. E/L/P-/- mice showed very little rolling after TNF-alpha, all of which was blocked by mAb to alpha4 integrin. Adherent and emigrated neutrophils were significantly reduced at 6 h after TNF-alpha. 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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