Avidity modulation activates adhesion under flow and requires cooperativity among adhesion receptors

Area of Science:

• Immunology
• Cell Biology
• Biophysics

Background:

• Leukocyte adhesion is crucial for immune responses and is regulated by integrin avidity.
• Cytoskeletal constraints limit integrin diffusion, impacting adhesion.
• Existing assays do not fully replicate in vivo conditions like blood flow and multiple adhesion molecule interactions.

Purpose of the Study:

• To investigate the effect of cytochalasin D on leukocyte-endothelial cell adhesion under flow conditions.
• To determine the role of integrin diffusion and ICAM-1 in this process.
• To explore the necessity of cooperativity between adhesion receptors.

Main Methods:

• Utilizing flow-based adhesion assays with leukocytes and endothelial cells.
• Employing cytochalasin D at concentrations that enhance integrin diffusion without altering cell morphology.
• Assessing the impact of ICAM-1 expression and functional cooperativity between adhesion molecules.

Main Results:

• Cytochalasin D significantly increased rolling and firmly adherent leukocytes, as well as the duration of both adhesion states.
• These effects were dependent on endothelial ICAM-1 expression.
• The beta2-integrin-ICAM-1 interaction alone was insufficient, highlighting the need for cooperativity.

Conclusions:

• Modulating integrin diffusion with cytochalasin D enhances leukocyte adhesion under flow.
• ICAM-1 is essential, but functional cooperativity among adhesion receptors is also required for optimal adhesion avidity.
• These findings provide insights into leukocyte trafficking in physiological settings.