Infectious susceptibility and severe deficiency of leukocyte rolling and recruitment in E-selectin and P-selectin double mutant mice

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Infectious susceptibility and severe deficiency of leukocyte rolling and recruitment in E-selectin and P-selectin double mutant mice

DC Bullard, EJ Kunkel, H Kubo, MJ Hicks, I Lorenzo, NA Doyle, CM Doerschuk, K Ley and AL Beaudet
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.

During the initial phase of the inflammatory response, leukocytes marginate and roll along the endothelial surface, a process mediated largely by the selectins and their ligands. Mice with mutations in individual selectins show no spontaneous disease and have mild or negligible deficiencies of inflammatory responses. In contrast, we find that mice with null mutations in both endothelial selectins (P and E) develop a phenotype of leukocyte adhesion deficiency characterized by mucocutaneous infections, plasma cell proliferation, hypergammaglobulinemia, severe deficiencies of leukocyte rolling in cremaster venules with or without addition of TNF-alpha, and an absence of neutrophil emigration at 4 h in response to intraperitoneal Streptococcus pneumoniae peritonitis. These mice provide strong evidence for the functional importance of selectins in vivo.
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Steeber, D. A., Campbell, M. A., Basit, A., Ley, K., Tedder, T. F. (1998). Optimal selectin-mediated rolling of leukocytes during inflammation in vivo requires intercellular adhesion molecule-1 expression. Proc. Natl. Acad. Sci. USA 95: 7562-7567 [Abstract] [Full Text]
Cines, D. B., Pollak, E. S., Buck, C. A., Loscalzo, J., Zimmerman, G. A., McEver, R. P., Pober, J. S., Wick, T. M., Konkle, B. A., Schwartz, B. S., Barnathan, E. S., McCrae, K. R., Hug, B. A., Schmidt, A.-M., Stern, D. M. (1998). Endothelial Cells in Physiology and in the Pathophysiology of Vascular Disorders. Blood 91: 3527-3561 [Full Text]
Jung, U., Ramos, C. L., Bullard, D. C., Ley, K. (1998). Gene-targeted mice reveal importance of L-selectin-dependent rolling for neutrophil adhesion. Am. J. Physiol. Heart Circ. Physiol. 274: H1785-H1791 [Abstract] [Full Text]
Pan, J., Xia, L., Yao, L., McEver, R. P. (1998). Tumor Necrosis Factor-alpha - or Lipopolysaccharide-induced Expression of the Murine P-selectin Gene in Endothelial Cells Involves Novel kappa B Sites and a Variant Activating Transcription Factor/cAMP Response Element. J. Biol. Chem. 273: 10068-10077 [Abstract] [Full Text]
Schmidt, K. N., Hsu, C. W., Griffin, C. T., Goodnow, C. C., Cyster, J. G. (1998). Spontaneous Follicular Exclusion of SHP1-deficient B Cells Is Conditional on the Presence of Competitor Wild-type B Cells. J. Exp. Med. 187: 929-937 [Abstract] [Full Text]
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