Rather than passively binding ligands via immunoreceptors, macrophages capture particles by repeated extension of actin-rich protrusions

Flannagan, Ronald S.

Grinstein, Sergio

Harrison, Rene E.

Jaqaman, Khuloud

Yip, Christopher M.

The Journal of Cell Biology

English

PubMed

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.Version of Recor

Harvard University - DASH

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.</jats:p

Ronald S. Flannagan

Rene E. Harrison

Christopher M. Yip

Khuloud Jaqaman

Sergio Grinstein

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Dynamic macrophage “probing” is required for the efficient capture of phagocytic targets

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