title: Atrial natriuretic peptide down-regulates neutrophil recruitment on inflamed endothelium by reducing cell deformability and resistance to detachment force.
abstract: BACKGROUND
  Recombinant atrial natriuretic peptide (ANP) is administered in patients with acute heart failure in Japan to improve renal function and hemodynamics, but its anti-inflammatory effect on activated leukocytes may also contribute to its therapeutic efficacy.
  
  
  OBJECTIVE
  Examine unconventional role of ANP in neutrophil adhesion to inflamed endothelium.
  
  
  METHODS
  Human neutrophils were perfused over endothelial monolayers in a microfluidic lab-chip assay. Cell rheology was assessed by micropipette aspiration to assess changes in cortical tension and viscosity. Fluorescence microscopy was applied to measure adhesive contact area and β2-integrin focal bond formation.
  
  
  RESULTS
  ANP inhibited neutrophil rolling and firm adhesion without influencing the upregulation of cellular adhesion molecules on endothelium or the regulation of high affinity CD18 and shedding of L-selectin during neutrophil activation. Exposed to fluid shear, integrin mediated arrest was disrupted with ANP treatment, which elicited formation of long tethers and diminished cell spreading and contact. This correlated with a ∼40% increase in neutrophil viscosity and a reduction in the adhesive footprint.
  
  
  CONCLUSIONS
  A decrease in cell deformation and neutrophil flattening with ANP results in fewer integrin bond clusters, which translates to higher tensile forces and impaired adhesion strengthening and cell detachment.
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, CA 95616, USA.
authors.forename: Vasilios A
authors.initials: VA
authors.lastname: Morikis
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, CA 95616, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Radecke
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, CA 95616, USA.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, CA 95616, USA.
authors.forename: Volkmar
authors.initials: V
authors.lastname: Heinrich
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, CA 95616, USA.|Department of Physiology and Membrane Biology, School of Medicine, University of California, Davis, CA 95616, USA.
authors.forename: Fitz-Roy
authors.initials: FR
authors.lastname: Curry
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, CA 95616, USA.
authors.forename: Scott I
authors.initials: SI
authors.lastname: Simon
mesh_terms: D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D018821:CD18 Antigens / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D019040:E-Selectin / Q000235:genetics / Q000378:metabolism; D004727:Endothelium / Q000166:cytology / Q000378:metabolism*; D018056:Hemorheology / Q000187:drug effects* / Q000502:physiology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D046210:Microfluidic Analytical Techniques; D008856:Microscopy, Fluorescence; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D033081:Shear Strength / Q000187:drug effects
chemical_list: D018821:CD18 Antigens; D019040:E-Selectin; C573420:ICAM1 protein, human; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1; D009320:Atrial Natriuretic Factor
keywords: Atrial natriuretic peptide; adhesion; inflammation; neutrophil