Linked regulation of motility and integrin function in activated migrating neutrophils revealed by interference in remodelling of the cytoskeleton.

摘要: Neutrophils migrate rapidly by co-ordinating regulation of their β2-integrin adhesion with turnover filamentous F-actin. The seven-protein Arp2/3 complex regulates actin polymerisation upon activation proteins the WASP-family. To investigate links between polymerisation, adhesion, and migration, we used a novel osmotic-shock method to load neutrophils peptides: (1) WASP-WA Scar-WA (which incorporate actin- Arp2/3-binding regions WASP Scar1), compete endogenous WASP-family members; (2) proline rich motifs (PRM) from ActA protein L. monocytogenes or vinculin, which bind vasodilator-stimulated phosphoprotein (VASP), regulator cytoskeleton assembly. In flow system, rolling-adherent were stimulated formyl tri-peptide. This caused rapid immobilisation, followed migration increasing velocity, supported activated CD11b/CD18. Loading PRM (but not vinculin PRM) concentration-dependent reduction in velocity. At highest concentration, unstimulated had elevated F-actin rigid, but could change content shape stimulation. also marked rate, lesser effect. did modify activation-dependent formation shape. However, rate downregulation integrin appeared contribute impaired migration. These studies show that interference cytoskeletal reorganisation follows neutrophils, can impair function as well motility. They suggest role migrating neutrophils. Cell Motil. Cytoskeleton 54:135–146, 2003. © 2003 Wiley-Liss, Inc.