Signaling for Defense

Abstract

Chen et al. studied the role of plastins in regulation of the integrin- and adhesion-dependent leukocyte respiratory burst, a defense response involving the generation of reactive oxygen species, and discovered that this response depended on cytoskeletal reorganization that took place independently of the reorganization involved in cell adhesion. Ligand binding to integrins, plasma membrane receptors involved in cell adhesion, activates signaling pathways that lead to reorganization of the actin cytoskeleton. This reorganization is critical to integrin-mediated cell adhesion. It is unclear whether integrin-mediated cytoskeletal reorganization leads directly to additional sequelae of integrin activation or other integrin-dependent downstream effects are secondary to integrin-mediated cell adhesion. Chen et al. used mutant mice lacking plastin 2 (LPL), a leukocyte-specific protein that cross-links actin in the cortical cytoskeleton, to distinguish between the roles of adhesion and of cytoskeletal reorganization in mediating an integrin-dependent leukocyte defense response. Polymorphonuclear leukocytes from LPL-deficient mice (LPL –/– PMNs ) showed normal migration, adhesion, and spreading, as well as integrin-dependent phagocytosis of Staphylococcus aureus , but failed to kill these bacteria or to generate an integrin- and adhesion-dependent respiratory burst. The authors used Western analysis to investigate signaling responses downstream of integrin ligation and found that LPL –/– PMNs were defective in activation of the tyrosine kinase Syk but showed normal phosphorylation of ERK. These data indicate that, in at least some integrin signaling pathways, integrin-mediated changes in cytoskeletal reorganization play a role that is independent of the integrin-mediated changes in the cytoskeleton required for cell adhesion and independent of adhesion itself. H. Chen, A. Mocsai, H. Zhang, R.-X. Ding, J. H. Morisaki, M. White, J. M. Rothfork, P. Heiser, E. Colucci-Guyon, C. A. Lowell, H. D. Gresham, P. M. Allen, E. J. Brown, Role for plastin in host defense distinguishes integrin signaling from cell adhesion and spreading. Immunity 19 , 95-104 (2003) [Online Journal]