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Analysis of CD97 expression and manipulation: Antibody treatment but not gene targeting curtails granulocyte migration

Item Type:Article
Title:Analysis of CD97 expression and manipulation: Antibody treatment but not gene targeting curtails granulocyte migration
Creators Name:Veninga, H. and Becker, S. and Hoek, R.M. and Wobus, M. and Wandel, E. and van der Kaa, J. and van der Valk, M. and de Vos, A.F. and Haase, H. and Owens, B. and van der Poll, T. and van Lier, R.A. and Verbeek, J.S. and Aust, G. and Hamann, J.
Abstract:The heptahelical receptor CD97 is a defining member of the EGF-TM7 family of adhesion class receptors. In both humans and mice, CD97 isoforms are expressed with variable numbers of tandemly arranged N-terminal epidermal growth factor-like domains that facilitate interactions with distinct cellular ligands. Results from treatment of mice with mAbs in various disease models have suggested a role for CD97 in leukocyte trafficking. Here, we aimed to thoroughly characterize the expression profile of CD97, and delineate its biological function. To this end, we applied a novel polyclonal Ab, which is the first antiserum suitable for immunohistochemistry, and combined this analysis with the study of Cd97-lacZ knock-in mice. We show that similar to the situation in humans, hematopoietic, epithelial, endothelial, muscle, and fat cells expressed CD97. Despite this broad expression pattern, the Cd97(-/-) mouse that we created had no overt phenotype, except for a mild granulocytosis. Furthermore, granulocyte accumulation at sites of inflammation was normal in the absence of CD97. Interestingly, application of CD97 mAbs blocked granulocyte trafficking after thioglycollate-induced peritonitis in wild-type but not in knock-out mice. Hence, we conclude that CD97 mAbs actively induce an inhibitory effect that disturbs normal granulocyte trafficking, which is not perturbed by the absence of the molecule.
Keywords:Antibodies, Cell Migration Inhibition, Gene Expression Regulation, Gene Targeting, Granulocytes, Immunophenotyping, Inflammation Mediators, Leukocytosis, Lung, Membrane Glycoproteins, Organ Specificity, Spleen, Animals, Mice
Source:Journal of Immunology
Publisher:American Association of Immunologists (U.S.A.)
Page Range:6574-6583
Date:1 November 2008
Official Publication:http://www.jimmunol.org/cgi/content/abstract/181/9/6574
PubMed:View item in PubMed

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