The human EGF-TM7 receptor EMR3 is a marker for mature granulocytes

Matmati, Mourad; Pouwels, Walter; Bruggen, Robin van; Jansen, Machiel H.; Hoek, Robert M.; Verhoeven, Arthur J.; Hamann, Jörg

doi:10.1189/jlb.0406276

Cited by 47 publications

(40 citation statements)

References 43 publications

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“…The tightly restricted expression of murine ADGRE1 (EMR1 or F4/80) has allowed its use as an excellent marker of resident murine tissue macrophages for over 30 years (Austyn and Gordon, 1981;Gordon et al, 2011). Human ADGREs (EGF-TM7 receptors) are useful markers for granulocytes, with ADGRE1 (EMR1) found on eosinophils and ADGRE3 (EMR3) on mature polymorphogenic granulocytes Matmati et al, 2007;Legrand et al, 2014). In contrast, ADGRE5 (CD97) is not restricted to myeloid cells but also found on lymphoid, epithelial, muscle, and other cell types (Eichler et al, 1994;Jaspars et al, 2001;Aust et al, 2006;Veninga et al, 2008;Zyryanova et al, 2014).…”

Section: Expressionmentioning

confidence: 99%

“…Furthermore, the entire GAIN domain was necessary and, as opposed to the GPS motif, sufficient for autoproteolysis (Arac et al, 2012b). Of note, the GAIN domain need not consist of two subdomains, as illustrated by members of the ADGRE (EGF-TM7) subfamily, which undergo proteolysis despite the lack of a subdomain A (Kwakkenbos et al, 2002;Stacey et al, 2002;Matmati et al, 2007).…”

Section: Autoproteolytic Processingmentioning

confidence: 99%

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International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G Protein–Coupled Receptors

et al. 2015

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Section: Expressionmentioning

confidence: 99%

Section: Autoproteolytic Processingmentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G Protein–Coupled Receptors

et al. 2015

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“…at a dose of 0.25 mg, 16 h before induction of sterile peritonitis. 3D7 is directed against human EMR3, a member of the EGF-TM7 family not present in mice (29). mAbs were produced under approved conditions of good laboratory practice at Organon Research Center USA.…”

Section: Thioglycollate-induced Peritonitismentioning

confidence: 99%

Analysis of CD97 Expression and Manipulation: Antibody Treatment but Not Gene Targeting Curtails Granulocyte Migration

Veninga

Becker

Hoek

et al. 2008

The Journal of Immunology

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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.

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“…1A). Hamster anti-human EMR3 Ab 3D7 was used as isotype control (21). An ELISA employing rabbit anti-hamster IgG (SouthernBiotech) and goat anti-hamster IgG-HRP (Serotec) was used to detect hamster IgGs in serum.…”

Section: Animals and Absmentioning

confidence: 99%

Therapeutic Antibody Targeting of CD97 in Experimental Arthritis: the Role of Antigen Expression, Shedding, and Internalization on the Pharmacokinetics of Anti-CD97 Monoclonal Antibody 1B2

Groot¹,

Vogel²,

Dulos³

et al. 2009

The Journal of Immunology

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CD97 is a member of the EGF-TM7 family of adhesion class receptors, with a proposed role in inflammatory cell recruitment. Neutralization of murine CD97 with the anti-mCD97 mAb 1B2 was efficacious in prevention of murine collagen-induced arthritis, a model with features resembling rheumatoid arthritis. Here, the therapeutic potential of neutralizing CD97 in arthritis was studied with emphasis on the 1B2 pharmacokinetics. Mice with established arthritis were treated with anti-mCD97 or anti-TNF-α serum. Ab pharmacokinetics and biodistribution were studied in diseased and nondiseased mice using labeled 1B2. The impact of CD97 expression on Ab pharmacokinetics was studied using CD97 knockout mice. Treatment with 1B2 showed an efficacy comparable to anti-TNF-α treatment. Pharmacokinetic analysis of 1B2 in wild-type and CD97 knockout mice indicated a dose-dependent Ab clearance, due to specific interaction with CD97. Biodistribution studies showed accumulation of 1B2 in spleen and lung. In vitro studies using murine splenocytes revealed that CD97 when bound to Ab was internalized. Moreover, soluble CD97 was detected in the supernatant, suggesting Ag shedding. Finally, in arthritic mice, higher levels of soluble CD97 were found and 1B2 treatment led to specific targeting of inflamed paws, resulting in a higher clearance rate of 1B2 in arthritic mice than in wild-type mice. In conclusion, our data support a therapeutic value of CD97 neutralization in experimental arthritis. The pharmacokinetic profile of the 1B2 Ab illustrates the complexity of Ab elimination from an organism and stresses the importance of understanding Ag-Ab interactions when developing therapeutic mAbs.

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The human EGF-TM7 receptor EMR3 is a marker for mature granulocytes

Cited by 47 publications

References 43 publications

International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G Protein–Coupled Receptors

International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G Protein–Coupled Receptors

Analysis of CD97 Expression and Manipulation: Antibody Treatment but Not Gene Targeting Curtails Granulocyte Migration

Therapeutic Antibody Targeting of CD97 in Experimental Arthritis: the Role of Antigen Expression, Shedding, and Internalization on the Pharmacokinetics of Anti-CD97 Monoclonal Antibody 1B2

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