Affinity, lateral mobility, and clustering contribute independently to beta 2-integrin-mediated adhesion

Area of Science:

• Cellular biology
• Immunology
• Biophysics

Background:

• Beta(2)-integrin-mediated adhesion is crucial for leukocyte activation in inflammation.
• Avidity modulation, independent of integrin conformation, contributes to adhesion via clustering or motion.
• The role of integrin diffusion in adhesion versus clustering is not fully understood.

Purpose of the Study:

• To differentiate the proadhesive effects of integrin affinity changes, clustering, and motion.
• To investigate the independent and combined roles of these factors in leukocyte adhesion.

Main Methods:

• Devised an experimental system to isolate integrin affinity, clustering, and motion.
• Used cytochalasin D (CD) to induce clustering and motion, Mn(2+) for high affinity, and cell fixation to halt motion.
• Compared adhesion in fixed and unfixed cells under various conditions.

Main Results:

• CD and Mn(2+) increased adhesion in both fixed and unfixed cells.
• Unfixed cells showed higher adhesion than fixed cells after CD treatment, despite similar clustering.
• Fixation inhibited integrin motion, while unfixed cells allowed continued diffusion, enhancing integrin/ICAM-1 interactions.

Conclusions:

• Integrin motion, in addition to clustering, significantly enhances beta(2)-integrin-mediated adhesion.
• Integrin motion increases adhesion kinetics by facilitating interactions with ligands like ICAM-1.
• Affinity changes and avidity effects (clustering and motion) are independent and additive contributors to integrin adhesion.