'Slings' enable neutrophil rolling at high shear

Area of Science:

• Immunology
• Cell Biology
• Biophysics

Background:

• Leukocytes roll along blood vessel walls.
• Neutrophils roll at high shear stress via cell flattening and rear tethers.
• Previous models suggested tether retraction after rolling.

Purpose of the Study:

• To investigate the behavior of membrane tethers during high shear stress neutrophil rolling.
• To elucidate the mechanism of shear-resistant leukocyte adhesion in inflammation.

Main Methods:

• In vivo studies using an acute inflammation model.
• In vitro experiments utilizing P-selectin and neutrophils.
• High-speed microscopy to observe cell-substrate interactions.

Main Results:

• Membrane tethers persist as 'slings' at the front of rolling neutrophils, not retracting.
• P-selectin glycoprotein ligand-1 (PSGL-1) is localized in patches on slings, while LFA-1 is broadly distributed.
• Slings undergo stepwise peeling from P-selectin substrates due to PSGL-1 patch failure under hydrodynamic forces.

Conclusions:

• Neutrophil rolling at high shear stress involves persistent 'slings' that create a cell-autonomous adhesive substrate.
• This 'step-wise peeling of slings' mechanism differs from prior 'tether pulling' models.
• Slings facilitate neutrophil adhesion and migration in inflammatory microenvironments.