In this study, we examined the relationship between the endothelial selectins (P-selectin and E-selectin) and whether they are critical for α4-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–α4-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 α4-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 α4-integrin–mediated leukocyte recruitment is entirely dependent upon endothelial selectins.
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17 March 1997
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March 17 1997
The Association between α4-Integrin, P-Selectin, and E-Selectin in an Allergic Model of Inflammation
Samina Kanwar,
Samina Kanwar
From the *Immunology Research Group, Department of Medical Physiology, University of Calgary, Calgary, Alberta T2N 4N1, Canada; ‡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
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Daniel C. Bullard,
Daniel C. Bullard
From the *Immunology Research Group, Department of Medical Physiology, University of Calgary, Calgary, Alberta T2N 4N1, Canada; ‡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
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Michael J. Hickey,
Michael J. Hickey
From the *Immunology Research Group, Department of Medical Physiology, University of Calgary, Calgary, Alberta T2N 4N1, Canada; ‡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
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C. Wayne Smith,
C. Wayne Smith
From the *Immunology Research Group, Department of Medical Physiology, University of Calgary, Calgary, Alberta T2N 4N1, Canada; ‡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
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Arthur L. Beaudet,
Arthur L. Beaudet
From the *Immunology Research Group, Department of Medical Physiology, University of Calgary, Calgary, Alberta T2N 4N1, Canada; ‡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
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Barry A. Wolitzky,
Barry A. Wolitzky
From the *Immunology Research Group, Department of Medical Physiology, University of Calgary, Calgary, Alberta T2N 4N1, Canada; ‡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
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Paul Kubes
Paul Kubes
From the *Immunology Research Group, Department of Medical Physiology, University of Calgary, Calgary, Alberta T2N 4N1, Canada; ‡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
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Samina Kanwar
From the *Immunology Research Group, Department of Medical Physiology, University of Calgary, Calgary, Alberta T2N 4N1, Canada; ‡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
Daniel C. Bullard
From the *Immunology Research Group, Department of Medical Physiology, University of Calgary, Calgary, Alberta T2N 4N1, Canada; ‡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
Michael J. Hickey
From the *Immunology Research Group, Department of Medical Physiology, University of Calgary, Calgary, Alberta T2N 4N1, Canada; ‡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
C. Wayne Smith
From the *Immunology Research Group, Department of Medical Physiology, University of Calgary, Calgary, Alberta T2N 4N1, Canada; ‡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
Arthur L. Beaudet
From the *Immunology Research Group, Department of Medical Physiology, University of Calgary, Calgary, Alberta T2N 4N1, Canada; ‡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
Barry A. Wolitzky
From the *Immunology Research Group, Department of Medical Physiology, University of Calgary, Calgary, Alberta T2N 4N1, Canada; ‡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
Paul Kubes
From the *Immunology Research Group, Department of Medical Physiology, University of Calgary, Calgary, Alberta T2N 4N1, Canada; ‡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
Address correspondence to Dr. Paul Kubes, Immunology Research Group, Department of Medical Physiology, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 4N1 Canada.
1Abbreviations used in this paper: Dv, venular diameter; dyn, dynes; PCA, passive cutaneous anaphylaxis; VCAM-1, vascular cell adhesion molecule 1.
Received:
September 18 1996
Revision Received:
December 12 1996
Online ISSN: 1540-9538
Print ISSN: 0022-1007
1997
J Exp Med (1997) 185 (6): 1077–1088.
Article history
Received:
September 18 1996
Revision Received:
December 12 1996
Citation
Samina Kanwar, Daniel C. Bullard, Michael J. Hickey, C. Wayne Smith, Arthur L. Beaudet, Barry A. Wolitzky, Paul Kubes; The Association between α4-Integrin, P-Selectin, and E-Selectin in an Allergic Model of Inflammation. J Exp Med 17 March 1997; 185 (6): 1077–1088. doi: https://doi.org/10.1084/jem.185.6.1077
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