Beta‐2 integrin mobility continues to contribute to increased adhesion after clustering is complete

β 2 integrins on leukocytes increase their adhesiveness both by affinity changes and avidity modulation. Avidity modulation, independent of integrin conformation changes, is usually thought to occur by rearrangement of the integrins into clusters. Theory predicts, however, that not only rearrangement, but also lateral mobility of the integrin can increase avidity, by increasing receptor‐ligand encounters, thereby increasing the kinetics of ligand binding. To determine whether continuing integrin motion plays a role in adhesion activation, we fixed cells after inducing integrin clustering, thereby freezing integrin motion. Fixed‐cell adhesion was less than that for live cells, even though the degree of integrin clustering was indistinguishable by confocal microscopy. For both live and fixed cells, integrins appeared to remain in a low affinity conformation, because integrin affinity could still be increased by treatment with Mn ++ . The simplest explanation for our results is that fixation prevents continued integrin motion on fixed cells, but integrins continue to diffuse on live cells (confirmed by diffusion measurements), increasing the kinetics of integrin/ICAM‐1 interactions and enhancing adhesion. This work was funded by NIH and VA grants.