title: The epidermal growth factor-seven transmembrane (EGF-TM7) receptor CD97 is required for neutrophil migration and host defense.
abstract: The epidermal growth factor-seven transmembrane (EGF-TM7) family is a group of seven-span transmembrane receptors predominantly expressed by cells of the immune system. Family members CD97, EGF module-containing mucin-like receptor (EMR) 1, EMR2, EMR3, EMR4, and EGF-TM7-latrophilin-related protein are characterized by an extended extracellular region with a variable number of N-terminal EGF-like domains. EGF-TM7 receptors bind cellular ligands as demonstrated by the interaction of CD97 with decay accelerating factor (CD55) and dermatan sulfate. Investigating the effect of newly generated mAb on the migration of neutrophilic granulocytes, we here report for the first time in vivo data on the function of CD97. In dextran sulfate sodium-induced experimental colitis, we show that homing of adoptively transferred neutrophils to the colon was significantly delayed when cells were preincubated with CD97 mAb. The consequences of this defect in neutrophil migration for host defense are demonstrated in a murine model of Streptococcus pneumoniae-induced pneumonia. Mice treated with CD97 mAb to EGF domain 1 (1B2) and EGF domain 3 (1C5) displayed a reduced granulocytic inflammatory infiltrate at 20 h after inoculation. This was associated with a significantly enhanced outgrowth of bacteria in the lungs at 44 h and a strongly diminished survival. Together, these findings indicate an essential role for CD97 in the migration of neutrophils.
authors.affiliation: Laboratory for Experimental Internal Medicine, Department of Pathology, Academic Medical Center, University of Amsterdam, 1100 DE Amsterdam, The Netherlands.
authors.forename: Jaklien C
authors.initials: JC
authors.lastname: Leemans
authors.forename: Anje A
authors.initials: AA
authors.lastname: te Velde
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.forename: Roelof J
authors.initials: RJ
authors.lastname: Bennink
authors.forename: Kora
authors.initials: K
authors.lastname: de Bruin
authors.forename: René A W
authors.initials: RA
authors.lastname: van Lier
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
authors.forename: Jörg
authors.initials: J
authors.lastname: Hamann
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000096:biosynthesis / Q000378:metabolism; D001666:Binding Sites, Antibody; D002460:Cell Line; D002465:Cell Movement / Q000276:immunology*; D003092:Colitis / Q000276:immunology / Q000473:pathology; D006224:Cricetinae; D004195:Disease Models, Animal; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D007113:Immunity, Innate; D007274:Injections, Intraperitoneal; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008562:Membrane Glycoproteins / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009503:Neutropenia / Q000276:immunology / Q000517:prevention & control; D020556:Neutrophil Infiltration / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000637:transplantation; D011018:Pneumonia, Pneumococcal / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D043562:Receptors, G-Protein-Coupled
chemical_list: C490633:Adgre5 protein, mouse; D000911:Antibodies, Monoclonal; D008562:Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; D066246:ErbB Receptors