Antje M Wengner

Publications (4)51.22 Total impact

• Article: Differential mobilization of subsets of progenitor cells from the bone marrow.

  Simon C Pitchford, Rebecca C Furze, Carla P Jones, Antje M Wengner, Sara M Rankin
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  ABSTRACT: G-CSF stimulates mobilization of hematopoietic progenitor cells (HPCs) from bone marrow by disrupting the CXCR4/SDF-1alpha retention axis. We show here that distinct factors and mechanisms regulate the mobilization of endothelial (EPCs) and stromal progenitor cells (SPCs). Pretreatment of mice with VEGF did not disrupt the CXCR4/SDF-1alpha chemokine axis but stimulated entry of HPCs into the cell cycle via VEGFR1, reducing their migratory capacity in vitro and suppressing their mobilization in vivo. In contrast, VEGF pretreatment enhanced EPC mobilization via VEGFR2 in response to CXCR4 antagonism. Furthermore, SPC mobilization was detected when the CXCR4 antagonist was administered to mice pretreated with VEGF, but not G-CSF. Thus, differential mobilization of progenitor cell subsets is dependent upon the cytokine milieu that regulates cell retention and proliferation. These findings may inform studies investigating mechanisms that regulate progenitor cell recruitment in disease and can be exploited to provide efficacious stem cell therapy for tissue regeneration.
  Cell stem cell 02/2009; 4(1):62-72. · 23.56 Impact Factor
• Article: The coordinated action of G-CSF and ELR + CXC chemokines in neutrophil mobilization during acute inflammation.

  Antje M Wengner, Simon C Pitchford, Rebecca C Furze, Sara M Rankin
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  ABSTRACT: In this study, we have identified a unique combinatorial effect of the chemokines KC/MIP-2 and the cytokine granulocyte colony-stimulating factor (G-CSF) with respect to the rapid mobilization of neutrophils from the bone marrow in a model of acute peritonitis. At 2 hours following an intraperitoneal injection of thioglycollate, there was a 4.5-fold increase in blood neutrophil numbers, which was inhibited 84% and 72% by prior administration of blocking mAbs against either the chemokines KC/MIP-2 or G-CSF, respectively. An intraperitoneal injection of G-CSF acted remotely to stimulate neutrophil mobilization, but did not elicit recruitment into the peritoneum. Further, in vitro G-CSF was neither chemotactic nor chemokinetic for murine neutrophils, and had no priming effect on chemotaxis stimulated by chemokines. Here, we show that, in vitro and in vivo, G-CSF induces neutrophil mobilization by disrupting their SDF-1alpha-mediated retention in the bone marrow. Using an in situ perfusion system of the mouse femoral bone marrow to directly assess mobilization, KC and G-CSF mobilized 6.8 x 10(6) and 5.4 x 10(6) neutrophils, respectively, while the infusion of KC and G-CSF together mobilized 19.5 x 10(6) neutrophils, indicating that these factors act cooperatively with respect to neutrophil mobilization.
  Blood 02/2008; 111(1):42-9. · 9.90 Impact Factor
• Article: CXCR5- and CCR7-dependent lymphoid neogenesis in a murine model of chronic antigen-induced arthritis.

  Antje M Wengner, Uta E Höpken, Peter K Petrow, Sven Hartmann, Uta Schurigt, Rolf Bräuer, Martin Lipp
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  ABSTRACT: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease with unknown etiology and only partially defined pathogenesis. The aim of this study was to establish a murine model of chronic arthritis in which the development of tertiary lymphoid tissue, a hallmark of human RA, is locally induced, and to characterize the roles of the homeostatic chemokine receptors CXCR5 and CCR7 in this process. We developed a modified model of chronic antigen-induced arthritis (AIA) in mice with a strong bias toward inflammation. Disease pathology was assessed up to 9 months in wild-type, CXCR5-deficient, and CCR7-deficient mice by determination of knee joint swelling and cellular and humoral immune responses, as well as by histologic analysis of arthritic knee joints. In this novel model of AIA, mice developed organized ectopic lymphoid follicles with topologically segregated B cell and T cell areas, high endothelial venules, and germinal center formation within the chronically inflamed synovial tissue. Analysis of the initiation and progression of AIA in wild-type, CXCR5-/-, and CCR7-/- mice revealed a reduction of acute inflammatory parameters in both knockout strains as well as significantly reduced joint destruction in CXCR5-/- mice. Most importantly, the development and organization of tertiary lymphoid tissue were significantly impaired in CXCR5-deficient and CCR7-deficient mice. Our results suggest that an inflammatory microenvironment efficiently triggers lymphoid neogenesis in autoimmune diseases such as RA. Moreover, the generation of autoreactive tertiary lymphoid tissues, which is entirely dependent on homeostatic chemokines, may in turn maintain local aberrant chronic immune responses.
  Arthritis & Rheumatism 11/2007; 56(10):3271-83. · 7.87 Impact Factor
• Article: CCR7 deficiency causes ectopic lymphoid neogenesis and disturbed mucosal tissue integrity.

  Uta E Höpken, Antje M Wengner, Christoph Loddenkemper, Harald Stein, Markus M Heimesaat, Armin Rehm, Martin Lipp
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  ABSTRACT: Homeostatic trafficking of lymphocytes through extralymphoid tissues has been recently observed, and a potential role in immune surveillance and the establishment of peripheral tolerance are considered. However, the mechanisms regulating lymphocyte recirculation through peripheral tissues under noninflammatory conditions are not well understood. Here, we demonstrate that the chemokine receptor CCR7 controls not only lymphocyte trafficking to and within secondary lymphoid organs but also homeostatic migration of T and B lymphocytes through nonlymphoid tissues. Lack of CCR7 results in a massive accumulation of lymphocytes in epithelial tissues. In particular, the gastrointestinal mucosal tissue of CCR7-/- mice is highly permissive for the formation of lymphoid aggregates, which develop into ectopic follicular structures with major topologic characteristics of lymph nodes. Flow cytometry analysis of CD4+ T cells derived from ectopic follicles revealed that CD44hiCD62Llo effector memory T cells predominate in the gastric lymphoid aggregates. In aged mice, lack of CCR7 induced age-dependent histomorphologic changes in the stomach with profound cystic hyperplasia and an increased rate of mucosal proliferation resembling Menetrier disease. Thus, CCR7 regulates the cellular organization of visceral tissue by governing life-long recirculation of naive and memory lymphocytes under homeostatic conditions.
  Blood 03/2007; 109(3):886-95. · 9.90 Impact Factor