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4-Integrin, P-Selectin, and
E-Selectin in an Allergic Model of Inflammation
By
From the * Immunology Research Group, Department of Medical Physiology, University of Calgary,
Calgary, Alberta T2N 4N1, Canada; In this study, we examined the relationship between the endothelial selectins (P-selectin and
E-selectin) and whether they are critical for Department of Comparative Medicine, University of Alabama
at Birmingham, Birmingham, Alabama 35294; § Department of Microbiology and Immunology,
Baylor College of Medicine, Houston, Texas 77030-2399; Department of Molecular and Human
Genetics, Baylor College of Medicine and Howard Hughes Medical Institute, Houston, Texas 77030;
and ¶ Department of Inflammation/Autoimmune Diseases, Hoffmann La-Roche Inc., Nutley, New
Jersey 07110-1199
4-integrin-dependent leukocyte recruitment in inflamed (late phase response), cremasteric postcapillary venules. Animals were systemically
sensitized and 2 wk later challenged intrascrotally with chicken ovalbumin. Leukocyte rolling
flux, adhesion, and emigration were assessed at baseline and 4 and 8 h postantigen challenge.
There was a significant increase in leukocyte rolling flux, adhesion, and emigration in sensitized
and challenged mice at both 4 and 8 h. At 8 h, the increase in leukocyte rolling flux was ~50%
inhibitable by an anti-4-integrin antibody, 98% inhibitable by fucoidin (a selectin-binding
carbohydrate), and 100% inhibitable by an anti-P-selectin antibody. P-selectin-deficient animals displayed no leukocyte rolling or adhesion at 8 h after challenge. However, at 8 h there
were many emigrated leukocytes in the perivascular space suggesting P-selectin-independent
rolling at an earlier time point. Indeed, at 4 h postantigen challenge in P-selectin-deficient mice,
there was increased leukocyte rolling, adhesion, and emigration. The rolling in the P-selectin-
deficient mice at 4 h was largely 4-integrin dependent. However, there was an essential E-selectin-
dependent component inasmuch as an anti-E-selectin antibody completely reversed the rolling, and in E-selectin and P-selectin double deficient mice rolling, adhesion and emigration
were completely absent. These results illustrate that P-selectin underlies all of the antigen-induced
rolling with a brief transient contribution from E-selectin in the P-selectin-deficient animals.
Finally, the antigen-induced 4-integrin-mediated leukocyte recruitment is entirely dependent
upon endothelial selectins.
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