title: Angiopoietin-2 promotes myeloid cell infiltration in a β₂-integrin-dependent manner.
abstract: In human inflammatory diseases, we identified endothelial angiopoietin-2 (Ang-2) expression to be strongly associated with inflammations mediated by myeloid cells but not lymphocytes. To identify the underlying mechanism, we made use of a transgenic mouse model with inducible endothelial cell-specific expression of Ang-2. In this model, in the absence of inflammatory stimuli, long-term expression of Ang-2 led to a time-dependent accumulation of myeloid cells in numerous organs, suggesting that Ang-2 is sufficient to recruit myeloid cells. In models of acute inflammation, such as delayed-type hypersensitivity and peritonitis, Ang-2 transgenic animals showed an increased responsiveness. Intravital fluorescence video microscopy revealed augmented cell adhesion as an underlying event. Consequently, we demonstrated that Ang-2 is able to induce strong monocyte adhesion under shear in vitro, which could be blocked by antibodies to β₂-integrin. Taken together, our results describe Ang-2 as a novel, endothelial-derived regulator of myeloid cell infiltration that modulates β₂-integrin-mediated adhesion in a paracrine manner.
authors.affiliation: Edinger Institute/Institute of Neurology, Frankfurt University Medical School, Frankfurt, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Scholz
authors.forename: Victoria
authors.initials: V
authors.lastname: Lang
authors.forename: Reinhard
authors.initials: R
authors.lastname: Henschler
authors.forename: Marcus
authors.initials: M
authors.lastname: Czabanka
authors.forename: Peter
authors.initials: P
authors.lastname: Vajkoczy
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Chavakis
authors.forename: Janina
authors.initials: J
authors.lastname: Drynski
authors.forename: Patrick N
authors.initials: PN
authors.lastname: Harter
authors.forename: Michel
authors.initials: M
authors.lastname: Mittelbronn
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Dumont
authors.forename: Karl H
authors.initials: KH
authors.lastname: Plate
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Reiss
mesh_terms: D000328:Adult; D042702:Angiopoietin-2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D018821:CD18 Antigens / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002448:Cell Adhesion / Q000235:genetics; D002465:Cell Movement / Q000235:genetics*; D002478:Cells, Cultured; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009000:Monocytes / Q000378:metabolism / Q000502:physiology; D022423:Myeloid Cells / Q000378:metabolism / Q000502:physiology*; D023461:Myeloid Progenitor Cells / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D042702:Angiopoietin-2; D018821:CD18 Antigens