Affinity, lateral mobility, and clustering contribute independently to beta 2-integrin-mediated adhesion.
Affinity changes and avidity modulation both contribute to activation of beta(2)-integrin-mediated adhesion, an essential, early step in inflammation. Avidity modulation, defined as an increase in adhesiveness independent of integrin conformational changes, might be due to integrin clustering, motion, or both. Increased integrin diffusion upon leukocyte activation has been demonstrated, but whether it is proadhesive in itself, or just constitutes a mechanism for integrin clustering, remains unclear. To understand the proadhesive effects of integrin affinity changes, clustering, and motion, an experimental system was devised to separate them. Clustering and integrin motion together were induced by cytochalasin D (CD) without inducing high-affinity; integrin motion could then be frozen by fixation; and high affinity was induced independently by Mn(2+). Adhesion was equivalent for fixed and unfixed cells except following pretreatment with CD or Mn(2+), which increased adhesion for both. However, fixed cells were less adhesive than unfixed cells after CD, even though integrin clustering was similar. A simple explanation is that CD induces both clustering and integrin motion, fixation then stops motion on fixed cells, but integrins continue to diffuse on unfixed cells, increasing the kinetics of integrin/ICAM-1 interactions to enhance adhesion. Affinity changes are then independent of, and additive to, avidity effects.
Yu
Tao
T
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Wu
Xing
X
Gupta
Kiran B
KB
Kucik
Dennis F
DF
D000818:Animals; D018821:CD18 Antigens / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D015638:Cytochalasin D / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D018821:CD18 Antigens; D015638:Cytochalasin D