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 α4 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.
Original language | English (US) |
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Pages (from-to) | 6755-6762 |
Number of pages | 8 |
Journal | Journal of Immunology |
Volume | 162 |
Issue number | 11 |
State | Published - Jun 1 1999 |
Externally published | Yes |
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology