Dynamic macrophage "probing" is required for the efficient capture of phagocytic targets.
Binding of ligands by immunoreceptors is thought to be a passive, stochastic process. Contrary to this notion, we found that binding of IgG-opsonized particles by Fcγ receptors was inhibited in macrophages, dendritic and microglial cells by agents that interfere with actin assembly or disassembly. Changes in the lateral mobility of the receptors--assessed by single-particle tracking--or in the microelasticity of the membrane--determined by atomic-force microscopy--could not account for the effects of actin disruption on particle binding. Instead, we found that the macrophages contact their targets by actively extending actin-rich structures. Formation of these protrusions is driven by Rac and requires phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate. Capture of C3bi-opsonized as well as unopsonized targets by macrophages was also dependent on actin. Thus, phagocytes continuously probe their environment for foreign particles in a manner akin to the constitutive sampling of the fluid milieu by dendritic cells. Active probing by phagocytes is most important when confronted by scarcely opsonized and/or highly mobile targets.
Program in Cell Biology, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
Ronald S
RS
Flannagan
Rene E
RE
Harrison
Christopher M
CM
Yip
Khuloud
K
Jaqaman
Sergio
S
Grinstein
D000818:Animals; D003713:Dendritic Cells / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D010587:Phagocytosis / Q000502:physiology*; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism
D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D017452:Receptors, IgG; C060974:phosphatidylinositol 3,4,5-triphosphate