title: Improved antibacterial host defense and altered peripheral granulocyte homeostasis in mice lacking the adhesion class G protein receptor CD97.
abstract: CD97 is a member of the adhesion family of G protein-coupled receptors. Alternatively spliced forms of CD97 bind integrins alpha5beta1 and alphavbeta3, decay accelerating factor, or dermatan sulfate. CD97 is expressed on myeloid cells at high levels and a variety of other cell types at lower levels. Little is known about the physiological function of CD97. To begin dissecting the function of CD97, we evaluated the immune response of CD97 null mice to systemic infection by Listeria monocytogenes. CD97 null mice were significantly more resistant to listeriosis than matched wild-type mice. A major determinant of the difference in survival appeared to be the comparatively more robust accumulation of granulocytes in the blood and in infected livers of CD97 null mice within 18 h of inoculation, correlating with a decrease in the number of bacteria. CD97 null mice also displayed a mild granulocytosis in the nonchallenged state. Because there is a strong suggestion that CD97 functions in an adhesive capacity, we examined the migratory properties of granulocytes in CD97 null mice. In chimeric animals, CD97 null and wild-type granulocytes migrated similarly, as determined by inflammation-induced emigration from the bone marrow and accumulation in the peritoneum. Granulocyte development in the bone marrow of CD97 null mice was comparable to that of wild-type mice, and CD97 deficiency did not appear to stimulate granulocytosis secondary to peripheral inflammation and resultant granulocyte colony-stimulating factor induction, unlike various other models of adhesion deficiencies. Our results suggest that CD97 plays a role in peripheral granulocyte homeostasis.
authors.affiliation: Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Linhua
authors.initials: L
authors.lastname: Tian
authors.forename: Makoto
authors.initials: M
authors.lastname: Haino
authors.forename: Ji-Liang
authors.initials: JL
authors.lastname: Gao
authors.forename: Ross
authors.initials: R
authors.lastname: Lake
authors.forename: Yvona
authors.initials: Y
authors.lastname: Ward
authors.forename: Hongshan
authors.initials: H
authors.lastname: Wang
authors.forename: Ulrich
authors.initials: U
authors.lastname: Siebenlist
authors.forename: Philip M
authors.initials: PM
authors.lastname: Murphy
authors.forename: Kathleen
authors.initials: K
authors.lastname: Kelly
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000172:deficiency* / Q000235:genetics*; D002465:Cell Movement / Q000276:immunology; D006098:Granulocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006706:Homeostasis / Q000235:genetics* / Q000276:immunology; D008088:Listeriosis / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D043562:Receptors, G-Protein-Coupled
chemical_list: C490633:Adgre5 protein, mouse; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D008562:Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled