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* Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
Research Laboratories, Center of Surgery, University of Leipzig, Leipzig, Germany;
Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands;
Department of Experimental Animal Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands;
¶ Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;
|| Molecular Muscle Physiology Group, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany; and
# Organon Research Center USA, Cambridge, MA 02142
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.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the Royal Netherlands Academy of Arts and Sciences, the Netherlands Organization for Scientific Research (NWO 814.02.012), the Landsteiner Foundation for Blood Transfusion Research (LSBR 0310), and the Medical Faculty of the University of Leipzig (research grant for graduation to S.B.).
2 H.V., S.B., and R.M.H. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. Jörg Hamann, Department of Experimental Immunology, K0-144, Academic Medical Center, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands. E-mail address: j.hamann{at}amc.uva.nl
4 Abbreviations used in this paper: EGF, epidermal growth factor; EMR, EGF module-containing mucin-like hormone receptor; hCD97, human CD97; mCD97, mouse CD97; TM7, seven-transmembrane; ES cell, embryonic stem cell; PFA, paraformaldehyde; F4, fourth generation; F8, eighth generation; F12, twelfth generation.
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