Neutrophil CD18-dependent arrest on intercellular adhesion molecule 1 (ICAM-1) in shear flow can be activated through...

Area of Science:

• Immunology
• Cell Biology
• Biophysics

Background:

• Neutrophil emigration is crucial for immune response, involving rolling, arrest, and transmigration.
• Selectins mediate initial rolling, while CD18 integrins are required for arrest and transmigration.
• Previous work showed L-selectin cross-linking activates CD18-dependent adhesion.

Purpose of the Study:

• To investigate if E-selectin and L-selectin binding can activate neutrophil CD18-dependent adhesion under shear flow.
• To determine the specific roles of L-selectin and E-selectin in initiating neutrophil arrest.

Main Methods:

• Co-transfection of human ICAM-1 and E-selectin into L cells.
• Quantification of neutrophil capture, rolling, and arrest using a parallel plate flow chamber at 2.0 dyne/cm² shear stress.
• Treatment of neutrophils with anti-L-selectin mAb, cross-linking, IL-8 stimulation, and blocking antibodies against LFA-1 and Mac-1.

Main Results:

• E-selectin supported neutrophil capture and rolling but did not induce CD18-mediated arrest.
• L-selectin cross-linking induced arrest in approximately 50% of neutrophils within 54 micrometers.
• Combined L-selectin cross-linking and subthreshold IL-8 significantly potentiated cell arrest.
• Neutrophil arrest involved both LFA-1 and Mac-1, with dual blockade reducing arrest to baseline levels.

Conclusions:

• L-selectin, but not E-selectin, can signal the transition from neutrophil rolling to cell arrest under shear flow.
• L-selectin activation is a key event in initiating firm neutrophil adhesion and subsequent transmigration.