title: Bradykinin shifts endothelial fluid passage from para- to transcellular routes.
abstract: The signalling peptide bradykinin (BK) is implicated in inflammation and angiogenesis. It promotes fluid transport from blood vessels to interstitial space, and thus facilitates oedema formation. To clarify whether paracellular or transcellular pathways mediate this effect, we investigated the BK-stimulated fluid transport across endothelial monolayers in vitro by comparison of electrical and fluorescence methods. Electrical cell impedance sensing monitored a biphasic response of cell layers to BK with high time resolution: a short decrease (18%, 1 min) was followed by a more sustained increase in paracellular resistance (30%, 10 min). The two phases can be assigned to second messengers of the BK-signalling pathway: Ca(2+) for the decrease and cyclic adenosine monophosphate for the rise of resistance, respectively. Despite tightening of the intercellular clefts, BK increased the fluid permeability by 39%, indicating transcellular fluid transport. Additionally, BK stimulated both in- and outwardly directed membrane trafficking as assessed by vesicular fluid uptake (by 49%) and secretion of von Willebrandt factor (by 85%). In conclusion, the combination of electrical and fluorescence data suggests that BK induces a shift from para- to transcellular fluid transport across endothelium.
authors.affiliation: Institute of Physiology II, University of Münster, Robert-Koch Str. 27b, 48149 Münster, Germany. chrth@uni-muenster.de
authors.forename: C
authors.initials: C
authors.lastname: Riethmüller
authors.forename: P
authors.initials: P
authors.lastname: Jungmann
authors.forename: J
authors.initials: J
authors.lastname: Wegener
authors.forename: H
authors.initials: H
authors.lastname: Oberleithner
mesh_terms: D001825:Body Fluid Compartments / Q000502:physiology*; D001920:Bradykinin / Q000502:physiology*; D002463:Cell Membrane Permeability / Q000502:physiology*; D002478:Cells, Cultured; D003911:Dextrans / Q000378:metabolism*; D017097:Electric Impedance; D004705:Endocytosis / Q000502:physiology; D004730:Endothelium, Vascular / Q000502:physiology*; D005089:Exocytosis / Q000502:physiology; D006801:Humans
chemical_list: D003911:Dextrans; D001920:Bradykinin