Atrial natriuretic peptide down-regulates neutrophil recruitment on inflamed endothelium by reducing cell deformability and resistance to detachment force

作者：Morikis Vasilios A; Radecke Chris; Jiang Yanyan; Heinrich Volkmar; Curry Fitz Roy; Simon Scott I^*

来源：Biorheology, 2015, 52(5-6): 447-463.

DOI：10.3233/BIR-15067

• Atrial natriuretic peptide
• neutrophil
• adhesion
• inflammation

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 beta(2)-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 similar to 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.

• 出版日期2015